Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients.

OBJECTIVE: To evaluate the clinical response and endometrial morphology during the implantation window on ovarian hyperstimulation with the aromatase inhibitor letrozole in infertile ovulatory women. DESIGN: Prospective trial in infertile patients. SETTING: Tertiary care hospital. PATIENT(S): Eight ovulatory infertile patient candidates for ovarian superovulation. INTERVENTION(S): Subjects were monitored in one control cycle. In the next cycle, they received letrozole 5.0 mg daily on days 3 through 7 after menses. MAIN OUTCOME MEASURE(S): Number of ovulatory follicles; dominant follicle diameter; endometrial thickness; hormonal profile of FSH, LH, E(2), A, T, and P; endometrial histological dating; and pinopode formation assessed by scanning electron microscopy. RESULT(S): Cycles stimulated with letrozole resulted in more ovulatory follicles than did natural cycles (mean +/- SD 2.0 +/- 0.9 vs. 1.0 +/- 0.0), which attained a greater preovulatory diameter (mean +/- SD 23.8 +/- 2.7 vs. 19.3 +/- 2.1 mm), with similar endometrial thickness at midcycle compared with spontaneous cycles. Endocrine profile of medicated cycles was characterized on day 7 by increased levels of LH (5.9 +/- 0.8 vs. 3.5 +/- 0.4 IU/mL), reduced E(2) (98.4 +/- 11.4 vs. 161.5 +/- 14.7 pmol/L), and elevated androgens. Preovulatory and midsecretory E(2) were similar to spontaneous cycle, and P levels during midluteal phase were significantly elevated (44.2 +/- 4.6 vs. 27.7 +/- 4.6 pmol/L). Endometrial morphology during the implantation window in letrozole-stimulated cycles was characterized by in-phase histological dating and pinopode expression on scanning electron microscopy. CONCLUSION(S): Letrozole induces moderate ovarian hyperstimulation in ovulatory infertile patients with E(2) levels similar to spontaneous cycles and higher midluteal P, leading to both a normal endometrial histology and development of pinopodes, considered to be relevant markers of endometrial receptivity.

Role of nitric oxide and bcl-2 family genes in the regulation of human endometrial apoptosis.

OBJECTIVE: To investigate the role of nitric oxide (NO) and death regulatory genes, bcl-2 and bax, in human endometria apoptosis. DESIGN: Expression of bcl-2, bax, NO synthases (NOS), and the apoptotic effect of L-arginine on endometrial explants in vitro. SETTING: Prospective study. PATIENT(S): Thirty-seven eumenorrheic women. INTERVENTION(S): Endometrial samples were obtained with Pipelle suction curette after women signed institutional informed consent forms. MAIN OUTCOME MEASURE(S): DNA fragmentation (TUNEL), immunohistochemistry, and reverse transcription polymerase chain reaction. RESULT(S): Apoptosis was detected in mid and late secretory endometria. L-arginine induced an increase in apoptosis in stroma (threefold), glands (eightfold), and surface epithelia (fourfold) in proliferative but not secretory endometria explants. Immunostaining of Bcl-2 was almost absent in the secretory endometria, whereas Bax increased in the stroma at the end of the menstrual cycle, coincident to the decrease in the bcl-2/bax mRNA relative ratio (P<.05) observed in secretory endometria. CONCLUSION(S): The induction of DNA fragmentation by L-arginine on proliferative endometria suggests that NO may be involved in the endometrial apoptotic process, whose control may be related predominantly to the changes of Bcl-2 expression.

Aspectos morfológicos comparados en la relación feto placentaria de ratas ovariectomizadas / Compared morphologic aspects of the feto-placental relationship in ovariectomized rats

De acuerdo a los resultados obtenidos y a la información bibliográfica revisada, en las ooforectomías bilaterales de 7 días se produce una lisis embrioplacentaria posiblemente por disminución de los niveles de progesterona, ante la ausencia de cuerpos lúteos, con inhibición total del embarazo y pérdida del contenido uterino. No sucede lo mismo en las ooforectomías bilaterales de 14 días, en las que al parecer los niveles de progesterona circulante producidas por la placenta son suficientes para mantener el embarazo, aunque no permititían alcanzar la madurez embriofetal y placentaria. En las ooforectomías unilaterales de 7 y 14 días es posible obtener embarazos de término, con fetos vivos, pero de menor desarrollo y masa corporal que los controles. Estos efectos están directamente relacionados con la precocidad de la ovariectomía. Las placentas, en cambio, mantienen en estos casos, proporcionalidad con los controles en aspecto, peso y diámetro. Finalmente se puede concluir que para obtener un feto de crecimiento y desarrollo normales, es imprescindible la presencia de ambos ovarios, al menos hasta el día 14 de la preñez, en tanto que la placenta alcanza mayor peso y diámetro en presencia de un solo ovario, cuando más temprana es la ovariectomía.