[Factors associated with survival at one year of life in neonates with severe congenital cardiopathy in A National Hospital in Peru]. / Factores asociados a la supervivencia al año de vida en neonatos con cardiopatía congénita severa en un Hospital Nacional de Perú.

OBJECTIVES.: To determine factors associated with survival in the first year of life in neonates with severe congenital heart disease treated in a national hospital in Peru. MATERIALS AND METHODS.: 160 children born between 2012 and 2015 with a diagnosis of severe congenital cardiopathy were studied and admitted to the Neonatology Service of the Edgardo Rebagliati Martins National Hospital of the Peruvian Social Security. The Kaplan-Meier method and the Log-Rank test were used in the survival analysis. Crude and adjusted analyses were performed using Cox regression models. RESULTS.: Fifty-two, point 5 percent (52.5%) of patients were male and the most frequent severe congenital cardiopathy was pulmonary atresia (26.3%). Thirty-three, point seven percent (33.7%) of patients died, with a 66.3% (IC95% 58.4-73.0) one-year survival. Prenatal diagnosis improved survival (HRa 0.54, 95% CI 0.30-0.98) while cyanotic cardiopathies (HRa 2.93, 95% CI 1.36-6.34) and the presence of another congenital anomaly (HRa 3.28, 95% CI 1.79-6.01) decreased it; these factors were also significant in a second model stratified by surgical treatment with the exception of the stratified model by complications where a prenatal diagnosis ceased to be significant. CONCLUSIONS.: Prenatal diagnosis increases survival from severe congenital heart disease. However, cyanotic heart diseases and other congenital anomalies, which decrease this chance, should be considered, if surgery is performed or complications occur.

OBJETIVOS.: Determinar los factores asociados a la supervivencia en el primer año de vida en neonatos con cardiopatía congénita severa atendidos en un hospital nacional de Perú. MATERIALES Y MÉTODOS.: Se estudiaron 160 niños nacidos entre el 2012 y 2015 con diagnóstico de alguna cardiopatía congénita severa que ingresaron al Servicio de Neonatología del Hospital Nacional Edgardo Rebagliati Martins del Seguro Social del Perú. En el análisis de supervivencia se utilizó el método de Kaplan-Meier y la prueba Log-Rank. Se realizaron análisis crudos y ajustados mediante modelos de regresión de Cox. RESULTADOS.: El 52,5% de los pacientes fueron de sexo masculino y la cardiopatía congénita severa más frecuente fue la atresia pulmonar (26,3%). El 33,7% de los pacientes fallecieron, siendo la supervivencia al año del 66,3% (IC95% 58,4-73,0). El diagnóstico prenatal mejoró la supervivencia (HRa 0,54, IC95%: 0,30-0,98) mientras que las cardiopatías de tipo cianóticas (HRa 2,93, IC95%: 1,36-6,34) y la presencia de otra anomalía congénita (HRa 3,28, IC95%: 1,79-6,01) la disminuyeron, estos factores fueron también significativos en un segundo modelo estratificado por tratamiento quirúrgico con excepción del modelo estratificado por complicaciones donde un diagnóstico prenatal dejó de ser significativo. CONCLUSIONES.: El diagnóstico prenatal incrementa la supervivencia ante una cardiopatía congénita severa y permitiría un tratamiento quirúrgico oportuno; sin embargo, se debe considerar que las cardiopatías de tipo cianóticas y la presencia de otras anomalías congénitas extracardíacas disminuyen la supervivencia si se realiza una intervención quirúrgica o se presentan complicaciones.

Factores asociados a la supervivencia al año de vida en neonatos con cardiopatía congénita severa en un Hospital Nacional de Perú / Factors associated with survival at one year of life in neonates with severe congenital cardiopathy in A National Hospital in Peru

RESUMEN Objetivos. Determinar los factores asociados a la supervivencia en el primer año de vida en neonatos con cardiopatía congénita severa atendidos en un hospital nacional de Perú. Materiales y métodos. Se estudiaron 160 niños nacidos entre el 2012 y 2015 con diagnóstico de alguna cardiopatía congénita severa que ingresaron al Servicio de Neonatología del Hospital Nacional Edgardo Rebagliati Martins del Seguro Social del Perú. En el análisis de supervivencia se utilizó el método de Kaplan-Meier y la prueba Log-Rank. Se realizaron análisis crudos y ajustados mediante modelos de regresión de Cox. Resultados. El 52,5% de los pacientes fueron de sexo masculino y la cardiopatía congénita severa más frecuente fue la atresia pulmonar (26,3%). El 33,7% de los pacientes fallecieron, siendo la supervivencia al año del 66,3% (IC95% 58,4-73,0). El diagnóstico prenatal mejoró la supervivencia (HRa 0,54, IC95%: 0,30-0,98) mientras que las cardiopatías de tipo cianóticas (HRa 2,93, IC95%: 1,36-6,34) y la presencia de otra anomalía congénita (HRa 3,28, IC95%: 1,79-6,01) la disminuyeron, estos factores fueron también significativos en un segundo modelo estratificado por tratamiento quirúrgico con excepción del modelo estratificado por complicaciones donde un diagnóstico prenatal dejó de ser significativo. Conclusiones. El diagnóstico prenatal incrementa la supervivencia ante una cardiopatía congénita severa y permitiría un tratamiento quirúrgico oportuno; sin embargo, se debe considerar que las cardiopatías de tipo cianóticas y la presencia de otras anomalías congénitas extracardíacas disminuyen la supervivencia si se realiza una intervención quirúrgica o se presentan complicaciones.

ABSTRACT Objectives. To determine factors associated with survival in the first year of life in neonates with severe congenital heart disease treated in a national hospital in Peru. Materials and Methods. 160 children born between 2012 and 2015 with a diagnosis of severe congenital cardiopathy were studied and admitted to the Neonatology Service of the Edgardo Rebagliati Martins National Hospital of the Peruvian Social Security. The Kaplan-Meier method and the Log-Rank test were used in the survival analysis. Crude and adjusted analyses were performed using Cox regression models. Results. Fifty-two, point 5 percent (52.5%) of patients were male and the most frequent severe congenital cardiopathy was pulmonary atresia (26.3%). Thirty-three, point seven percent (33.7%) of patients died, with a 66.3% (IC95% 58.4-73.0) one-year survival. Prenatal diagnosis improved survival (HRa 0.54, 95% CI 0.30-0.98) while cyanotic cardiopathies (HRa 2.93, 95% CI 1.36-6.34) and the presence of another congenital anomaly (HRa 3.28, 95% CI 1.79-6.01) decreased it; these factors were also significant in a second model stratified by surgical treatment with the exception of the stratified model by complications where a prenatal diagnosis ceased to be significant. Conclusions. Prenatal diagnosis increases survival from severe congenital heart disease. However, cyanotic heart diseases and other congenital anomalies, which decrease this chance, should be considered, if surgery is performed or complications occur.

Antenatal diagnosis of a third trimester interstitial pregnancy: a case report.

Interstitial pregnancy cases that advance to term, or near term, are occasionally reported. We present an unusual case of a third trimester interstitial pregnancy with antenatal diagnosis and expectant management. She presented at 20 weeks of pregnancy with an early preterm premature rupture of membranes, and expectant management was initiated. The ultrasound suggested an interstitial location and a posterior magnetic resonance image, obtained at 26 weeks, confirmed the diagnosis. Because of the risk of uterine rupture, an elective cesarean section was performed at 28 weeks. During the laparotomy, the uterine fundus appeared intact with an asymmetric bulge that provided evidence of placenta increta. The baby was delivered, and an obstetric hysterectomy was performed. The newborn was admitted to the neonatal intensive care unit with a severe respiratory distress syndrome. No response to mechanical ventilation was observed, and neonatal death was reported. A uterine pathological examination confirmed the diagnosis.

Neuroendocrinology and ovarian aging.

The ovarian aging, a dynamic process that precedes the clinical manifestations of menopause, can be assessed using ovarian reserve biomarkers. It is well-known that reproduction during the later years of reproductive life has known limitations that challenge the success of assisted reproduction. Therefore, a review of the neuroendocrine modifications during this critical period of reproductive life may help to elucidate the ovarian aging process and its impact on reproduction. In this review, we aim to further the discussion of neuroendocrine changes taking place during the ovarian aging process that may impact reproductive function.

The human corpus luteum: life cycle and function in natural cycles.

OBJECTIVE: To summarize recent advances in the understanding of the endocrine signaling pathways between the hypothalamus, pituitary, and human corpus luteum (CL); to examine the major paracrine and autocrine mechanisms and the key genes and proteins involved in CL development, function, and regression in natural cycles; to review the endocrine and molecular response of the midluteal phase CL to in vivo administration of human chorionic gonadotropin (hCG); and to describe the ultrasonographic and Doppler evaluation of the ovary and endometrium throughout the luteal phase. DESIGN: Published data in the literature, including the basic and clinical research studies of the authors. SETTING: University-affiliated hospital and research centers. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical and molecular analysis of human CL function. RESULT(S): The endocrine function of the subpopulations of luteal cells is critical for the maintenance of CL function, including neovacularization and steroid hormones production. We consider the key genes and proteins that favor development of luteal structure and function throughout the menstrual cycle and in our model of hCG treatment resembling early pregnancy. CONCLUSION(S): These data indicate that the functional lifespan of the CL depends on paracrine and autocrine mechanisms. Therefore, the significance of the key genes and proteins that we analyze in lutein cells during CL development, function, demise, and rescue by hCG is likely to bring new therapeutic applications for the management of fertility defects and the control of fertility.

Pharmacokinetics and endometrial tissue levels of levonorgestrel after administration of a single 1.5-mg dose by the oral and vaginal route.

OBJECTIVE: To determine the pharmacokinetics and endometrial tissue levels of levonorgestrel when taken as a single dose of 1.5 mg either orally or vaginally by healthy women in the periovulatory phase of their menstrual cycle. DESIGN: Prospective randomized study. SETTING: Academic research institution. PATIENT(S): Thirty women with regular cycles allocated to control (n = 5), oral (n = 13), and vaginal (n = 12) groups. INTERVENTION(S): Blood samples were drawn before (0 time) and at 0.5, 1, 2, 4, 6, 8, 24, 48, and 168 hours after levonorgestrel administration. Endometrial samples were collected 24 and 168 hours after levonorgestrel administration. MAIN OUTCOME MEASURE(S): Plasma and endometrial tissue levels of levonorgestrel. RESULT(S): Plasma concentrations of levonorgestrel were significantly greater during the first 48 hours after oral administration. However, 7 days after levonorgestrel administration, the plasma levels were similar for both treatments (3-5 nmol/L). Compared with vaginal administration, oral administration resulted in higher peak plasma concentrations (Cmax 64 vs. 10.7 nmol/L), with a shorter time to reach the maximal concentrations (Tmax 1.4 vs. 6.6 hours) and with a greater AUC (509 vs. 175 nmol/L). Interestingly, the half-life of levonorgestrel was shorter after oral administration (25 hours vs. 32.6 hours). Levonorgestrel tissue concentrations were not related to the plasma levels. Levonorgestrel values tended to be higher in endometrial tissue after vaginal administration. The ratio between plasma and endometrial concentrations of levonorgestrel differed significantly between the groups. CONCLUSION(S): These data indicate that orally administered levonorgestrel achieves higher plasma levels sooner than vaginally administered levonorgestrel. However, plasma levels after vaginal administration are more sustained and were likely to be sufficient for ovarian suppression. Therefore, the vaginally administered levonorgestrel could be considered as an alternative option for emergency contraception.

[P450Arom and estrogenic microenvironment of eutopic endometria in endometriosis]. / P450Arom y microambiente estrogénico en endometrios eutópicos de mujeres con endometriosis.

BACKGROUND: Endometriosis, a common gynecologic disorder characterized by endometrial glands and stroma outside the uterus, is diagnosed by direct visualization of peritoneal and ovarian implants during laparoscopy. AIM: To study the estrogenic microenvironment in eutopic endometria of women with and without endometriosis. PATIENTS AND METHODS: Eutopic endometria, obtained during laparoscopy from 23 women with endometriosis and 20 fertile cyclic women undergoing tubal sterilization, was studied. P450Arom mRNA expression (RT-PCR) was measured. Also, P450Arom activity was assessed measuring testosterone conversion to estradiol and the concentration of this last hormone in cultured endometrial explants. RESULTS: Age and body mass index was similar in both groups studied. Seventy nine percent of endometria from women with endometriosis and in 29.4% from control group expressed P450Arom mRNA (p <0.01). The intensity of the band was higher in secretory endometria from women with endometriosis when compared to controls (p <0.01), but it was similar during the proliferative phase. Estradiol secretion to the culture media by proliferative endometria explants from women with endometriosis was 3-fold higher than secretory endometria (p <0.01) and endometria from control women in both phases. P450Arom activity, in the presence of testosterone, was 7-fold higher in endometrial cultures from women with endometriosis, when compare with the basal culture (p <0.01). However, in endometrial explant cultures from control women, this activity was not statistical different. CONCLUSIONS: These results indicate that in women with endometriosis, the microenvironment in the endometria is estrogenic as a consequence of an increased expression and activity of the P450Arom.

Expression of steroid receptors and proteins related to apoptosis in endometria of women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the expression of steroid hormone receptors, proteins related to apoptosis, and cell proliferation in endometria from women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Hospital research unit. PATIENT(S): Eight women with PCOS and 12 fertile healthy women of similar age to those with PCOS. INTERVENTION(S): Endometrial samples were obtained from women with PCOS (PCOSE) and normal (NE) women during the proliferative phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Expression studies (immunohistochemistry and reverse transcription-polymerase chain reaction) and DNA fragmentation [TdT-mediated dUTP nick end labeling (TUNEL)]. RESULT(S): In stroma, protein expression of estrogen receptor alpha, Bcl-2, and Bax was higher in PCOSE than in NE; epithelial cells had a greater expression of androgen receptor in the nucleus and a lower expression in the cytoplasm of PCOSE. Cell proliferation was higher in the epithelia of NE, while the expression of caspase-3 and DNA fragmentation was similar in both groups. The bax mRNA expression was higher in PCOSE, and bcl-2 mRNA expression was similar between groups. A higher bcl-2/bax relative ratio in PCOSE was observed. CONCLUSION(S): An alternating expression of proteins related to cell survival in endometria from PCOSE may potentially be associated with the disruption of their endometrial cell cycle.

The steroidogenic response and corpus luteum expression of the steroidogenic acute regulatory protein after human chorionic gonadotropin administration at different times in the human luteal phase.

This study was designed 1) to assess corpus luteum (CL) steroidogenesis in response to exogenous human chorionic gonadotropin (hCG) at different times during the luteal phase, 2) to examine the effect of hCG on steroidogenic acute regulatory protein (StAR) expression within the CL, 3) to correlate StAR expression and luteal steroidogenic responses to hCG, and 4) to determine whether endogenous LH regulates ovarian steroidogenesis in the early luteal phase. Blood was collected before and after hCG treatment for steroid and hCGbeta determinations. CL were obtained at the time of surgery to assess StAR gene and protein expression. During the early luteal phase various women received the GnRH antagonist for 24-48 h; some of them also received hCG 24 h after the GnRH antagonist. A slight steroidogenic response to hCG was observed in early luteal phase; 17alpha-hydroxyprogesterone, but not progesterone (P4), levels were significantly increased 8 h post-hCG, indicating a differential response by the granulosa and theca-lutein cells. The 1.6- and 4.4-kb StAR transcripts and the 37-kDa preprotein and 30-kDa mature StAR protein did not change post-hCG administration in early luteal phase CL. In contrast, the StAR 4.4- and 1.6-kb transcripts diminished significantly (P < 0.05) after the antagonist treatment. Immunohistochemical staining for StAR protein was weak, particularly in granulosa-lutein cells. Treatment with hCG restored StAR mRNA and protein and plasma P4 levels within 24 h in antagonist-treated women. hCG stimulated the highest plasma concentrations of P4 and estradiol in the midluteal phase, indicating its greatest steroidogenic capacity. Midluteal tissue StAR gene and protein expression increased by 1.6- and 1.4-fold after 24 h of hCG treatment, respectively. Administration of hCG resulted in the greatest increment in plasma P4 (4-fold) and 17alpha-hydroxyprogesterone (3-fold) levels over baseline in the late luteal phase. This was associated with an increase in StAR mRNA (3.5-fold) and protein (1.8-fold). Collectively, these data indicate that 1) the hCG-stimulated steroidogenic response is dependent on the age of the CL; 2) the early luteal phase CL is relatively insensitive to exogenous hCG in the presence of normal pituitary gonadotropin support, but becomes responsive when the latter is withdrawn; 3) the hCG-stimulated steroidogenic response in the mid- and late luteal phase is correlated with increased StAR mRNA and protein abundance; and 4) there are differential responses of small and large luteal cells to hCG stimulation that depend upon the age of the CL.

Criopreservacion de pronucleos: rol en el programa de fertilizacion asistida

Objetivo: Determinar el rol de la criopreservación (CP) de pronúcleos (PN), como una herramienta para disminuir la incidencia de embarazos múltiples y dar otra oportunidad de transferencia embrionaria, sin requerir estimulación ovárica nuevamente, en parejas con infertilidad que requieren como tratamiento algún tipo de procedimiento de Fertilización Asistida (FA). Material y Método: Se analizaron los resultados de 545 procedimientos de FA entre marzo del 2000 y junio del 2003. Resultados: La incorporación de la CP se logra en diciembre del 2001, criopreservando hasta la fecha el 51,3% de las parejas que tiene más de 6 folículos a aspirar. Se han criopreservado 623 PN dando un promedio 6,4 PN por pareja. Se han descongelado 166 PN, sobreviviendo 134 PN, lo que implica un 80,7%. Ciento catorce PN clivaron a embrión de 4 células, equivalente a un 85,1%. Se han transferido 114 PN en 39 ciclos con un promedio de 2,9 embriones por pareja, dando origen a 12 embarazos clínicos (30,7%) con una tasa implantacional del 11,4%. Se observa una reducción del número de embarazos múltiples en dobles del 23% al 15,5%, en triples del 7,6% al 2,2% y la no ocurrencia de cuádruples o más, al comparar el período 2000-diciembre 2001 (sin CP de PN), con diciembre de 2001-junio del 2003.

Molecular regulation of progesterone secretion by the human corpus luteum throughout the menstrual cycle.

The present study examines the expression of the steroidogenic acute regulatory protein (StAR) within the human corpus luteum (CL) in conjunction with other molecules that regulate the apoptotic process of the CL. Our results indicate that the primary 1.6 kb StAR transcript occurs in greater abundance in early and mid-luteal phase compared with late luteal phase CL. Mature StAR protein (30 kDa) was present in lower amounts within late CL compared with early and mid-luteal phase. The pre-protein (37 kDa), which has been considered the active isoform to favor cholesterol translocation and subsequently steroid hormone synthesis, was also detected in lower amount in late CL. Several molecules, including pro-inflammatory cytokines, reactive oxygen species, steroids and inducible nitric oxide synthase (iNOS), have been linked as pro-apoptotic regulatory agents. Moreover, many of these molecules diminish progesterone synthesis in human cultured luteal cells. Interestingly, these molecules preferentially decrease progesterone biosynthesis in mid and late luteal cells in culture. These data suggest that the inhibitory effect of these molecules, as well as the amount of apoptotic cells in the CL are age dependent. The number of luteal apoptotic cells, as well as luteal cells stained positive for iNOS, increased from early to late CL. To examine the effects of hCG on StAR expression and apoptosis, we used two models-(1) in vivo hCG administration during the late luteal phase; and (2) in vitro incubation of explants of late CL with hCG. hCG increased both the level of StAR expression and the level of anti-apoptotic protein Bcl-2 within the late CL. We conclude that mRNA and protein expression of StAR and bcl-2 are important target elements for hCG during the CL rescue.