Fatores prognósticos em terapia de reprodução assistida: hormônio anti-mülleriano e secreção endometrial de urocortina

Abstract

Objectives: Evaluate the accuracy of prognostic factors in assisted reproduction therapy analyzing ovarian reserve by antral follicle count and serum levels of anti-müllerian hormone and endometrial receptivityby dosage of lavage urocortin and endometrial biopsy, following the specific objectives: (1) Investigate if the antral follicle count and anti-müllerian hormone serum levels, as well as the dosage of lavage urocortin and endometrial biopsy, measured in the previous month to the assisted reproduction cycle are different in patients who subsequently obtained a pregnancy compared to the ones that did not obtain pregnancy; (2) Evaluate the stability of the anti-müllerian hormone dosage during the menstrual cycle, comparing values in two distinct moments of the cycle; (3) Evaluate the sensibility and specificity of the three tests (antral follicle count, anti-müllerian hormone and urocortin) in predicting pregnancy in women submitted to assisted reproduction therapy. Material and methods: Prospective study developed in the Laboratório de Reprodução Humana Professor Aroldo Fernando Camargos do Hospital das Clínicas da UFMG. Patients: Patients admitted for accomplishment of FIV/ICSI. Methods: (1) Antral follicle count on the 3rd day of the menstrual cycle by endovaginal ultrasound (135 patients); (2) Dosage of the anti-müllerian hormone in peripheral blood, collected on the 3rd and between the 18th and 20th days of the cycle using ELISA kits (135 patients); (3) Endometrial lavage urocortin dosage collected between the 18th and 20th days of the cycle using ELISA kits (102 patients); (4) Quantification of the urocortin and receptors CRH-R1 and CRH-R2 gene expression by Real time PCR in samples collected between the 18th and 20th days of the cycle (55 patients). Results: (1) The global pregnancy rate was of 21,48% and 25,89% when considering only patients who accomplished ovarian collection. The spontaneous abortion rate was of 34,5%; (2) There was a predominance of primary infertility (74,5% among non-pregnant NG and 62,1% among pregnants-G); (3) The main cause of infertility was the masculine factor (45,3%-NG and 65,5%-G); (4) There was no significant difference among ages (p=0,122), time of infertility (p=0,289), FSH dosed on the 3rd day of the cycle (p=0,522), gonadotropins dosage used (p=0,119), antral follicle count (p=0,350) and endometrial thickness (p=0,498) between patients who got pregnant and who did not; (5) There was significant difference in the number of oocytes (5,0-NG X 7,0-G; p = 0,013) and number of embryos (3,42-NG X 4,0-G; p = 0,013) between patients who got pregnant and who did not; (6)The AMH dosages on the 3rd and between the 18th and 20th days of the cycle were significantly higher in patients who got pregnant (p = 0,006 e p = 0,001). There was no significant difference between the two dosages of AMH from the same patient. The AMH dosage of 1,15ng/ml, collected between the 18th and 20th days of the cycle, predicts the occurrence of pregnancy with a 70% specificity and 62,1% sensibility; (7) The urocortin relative gene expression was 20% higher in endometrial samples of patients who got pregnant, but the endometrial lavage urocortin dosage did not show significant difference between the groups (p=0,688); (8) No significant alteration was observed in the gene expression of CRH-R1 and CRH-R2 in pregnant compared to non-pregnant patients (p = 0,1892 e p= 0,1923). Conclusions: (1) The antral follicle count is a good predictor for the number of oocytes and embryos obtained in FIV treatments. It is not a good predictor for pregnancy occurrence and a cutoff value cannot be established and used as a pre-treatment tracking exam; (2) The anti-müllerian hormone dosage is a good predictor for the pregnancy occurrence in FIV treatments being significantly higher in patients who got pregnant. The AMH concentrations are stable during the menstrual cycle and the exam can be collected at any moment of the cycle. Values over 1,15ng/ml determine higher pregnancy chance with specificity of 70% and sensibility of 62,1%; (3) The endometrial urocortin gene expression was 20% higher in patients who got obtained pregnancy after FIV treatments. The dosage of endometrial lavage using ELISA did not present enough sensibility to be used as a marker of endometrial receptivity in FIV treatments.