Correlation between endometrial dating of luteal phase days 6 and 10 of the same menstrual cycle

CONTEXT: Endometrial maturation, important in the diagnosis of infertile couples, has been evaluated since 1950 using the Noyes criteria. Nevertheless, there is no consensus regarding the most suitable period of the luteal phase for performing the biopsy. OBJETIVE: This study evaluated the correlation between the histological dating of two endometrial biopsies performed in the same menstrual cycle, on luteal phase days six and ten.DESIGN: Prospective study. SETTING: Human Reproduction Division of the Federal University of São Paulo, referral center. PATIENTS:Twenty-five women complaining of infertility had their menstrual cycles monitored by ultrasound and LH plasma levels, to obtain evidence of ovulation. PROCEDURES: Endometrial biopsies were performed on luteal phase days LH+6 and LH+10 (luteal phase day 1 = LH+1 = the day that follows LH peak). Dating was done according to morphometric criteria, in which an endometrium sample is considered out of phase if the minimum maturation delay is one day. On day LH+6, blood was drawn for plasma progesterone level determination. RESULTS: All patients had an ovulatory cycle (mean LH peak: 47.4 U/L; mean follicular diameter on LH peak day: 18.9 mm; mean endometrial thickness on LH peak day: 10.3 mm; mean plasma progesterone level on day LH+6: 14.4 ng/ml). 14 patients had both biopsies in phase; 5 patients had out of phase biopsies only on day LH+6; 3 had out of phase biopsies only on day LH+10 and 3 patients had out of phase biopsies on both days. McNemar's test showed no statistical difference between these data (p>33.36%). CONCLUSIONS: The correlation found between the endometrial datings suggests that biopsies performed on either of these two days are suitable for evaluation of endometrial maturation.CONTEXTO: A verificação da maturidade endometrial, elemento diagnóstico necessário na avaliação do casal com queixa de infertilidade, vem sendo feita desde 1950 através do critério de datação histológica de Noyes. No entanto, não existe um consenso em relação ao período da fase lútea mais adequado para a colheita. OBJETIVO: Avaliar a correlação entre as datações histológicas de duas amostras de endométrio colhidas nos dias 6 e 10 da fase lútea de um mesmo ciclo menstrual. LOCAL: Setor de Reprodução Humana da Universidade Federal de São Paulo (UNIFESP). TIPO DE ESTUDO: Estudo prospectivo. Constou da comparação entre duas datações de endométrio num mesmo ciclo menstrual. PARTICIPANTES: 25 pacientes com queixa de infertilidade tiveram um ciclo menstrual monitorizado por ultra-sonografia e medida plasmática de LH, para demonstração de ovulação. PROCEDIMENTO: Biópsias de endométrio foram feitas nos dias LH+6 e LH+10 da fase lútea, considerando-se o dia seguinte ao do pico de LH como LH+1. A datação foi feita de acordo com critério morfométrico, considerando-se o endométrio como fora de fase, se o atraso de maturação mínimo fosse de um dia. No dia LH+6 foi feita dosagem de progesterona plasmática. RESULTADOS: Todas as pacientes apresentaram ciclos ovulatórios (média dos valores de pico de LH: 47,3 U/L; média dos diâmetros foliculares no dia do pico de LH: 18,9 mm; média das espessuras do endométrio no dia do pico de LH: 10,3 mm; média das concentrações de progesterona plasmática no dia LH+6: 14,4 ng/ml.). Em 14 pacientes, as duas biópsias estavam em fase. Houve atraso de maturação apenas no dia LH+6 em cinco pacientes; apenas no dia LH+10 em três pacientes e, nos dois dias, em três pacientes. Não houve diferença estatística entre esses valores (teste de McNemar, p=33,36%). CONCLUSÕES: Os resultados sugerem que a colheita do endométrio em qualquer dos dias (sexto ou décimo) da fase lútea fornece resultados semelhantes em relação à maturidade endometrial.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women

Endometriosis is a disorder that affects 5% of the normal population but is present in up to 40% of women with pelvic pain and/or infertility. Recent evidence suggests that the endometrium of women with endometriosis exhibits progesterone insensitivity. One endometrial protein that fluctuates in response to progesterone is the estrogen receptor-alpha (ER alpha), being down-regulated at the time of peak progesterone secretion during the window of implantation. Here we demonstrate that the biomarker of uterine receptivity, beta 3 integrin subunit, is reduced or absent in some women with endometriosis and that such defects are accompanied by inappropriate over-expression of ER alpha during the mid-secretory phase. Using a well-differentiated endometrial cell line we showed that the beta 3 integrin protein is negatively regulated by estrogen and positively regulated by epidermal growth factor (EGF). By competing against estrogen with various selective estrogen receptor modulators (SERMs) and estrogen receptor agonists and antagonists, inhibition of expression of the beta 3 integrin by estrogen can be mitigated. In conclusion, we hypothesize that certain types of uterine receptivity defects may be caused by the loss of appropriate ER alpha down-regulation in the mid-secretory phase, leading to defects in uterine receptivity. Such changes might be effectively treated by timely administration of the appropriate anti-estrogens to artificially block ER alpha and restore normal patterns of gene expression. Such treatments will require further clinical studies