Efectos demográficos, clínicos y biológicos de la postergación de la maternidad / Demographic, clinical, and biological effects of delayed maternity

En el presente artículo se analizan los efectos de la postergación de la maternidad en tres ámbitos: i) demográfico, ii) clínico y iii) biológico. Desde luego, la literatura demográfica existente procede fundamentalmente de países con un buen grado de desarrollo, pero se ha realizado un esfuerzo por reunir la mayor cantidad de datos de países en desarrollo. Así se analiza la situación en Europa, EE.UU. y Latinoamérica para finalizar esta sección con la realidad específica en Chile. Desde el punto de vista clínico, se pone especial interés en los cambios que experimenta la probabilidad de embarazo por ciclo (definida como fecundabilidad) y la fertilidad en general. En los aspectos perinatológicos se enfatiza el incremento de frecuencia de la muerte fetal in útero temprana (aborto espontáneo) y tardía con especial mención de algunas patologías (frecuencia del síndrome de Down y otros). Se establece además la frecuencia significativamente mayor de bajo y muy bajo peso de nacimiento, necesidad de hospitalización del recién nacido (morbilidad perinatal) así como el efecto sobre la mortalidad neonatal.Biológicamente la postergación de la maternidad tiene su correlato en la pérdida de reserva ovárica y la disminución de la calidad ovocitaria que involucra un aumento en la incidencia de fallas de fecundación y embriones con bajo potencial de desarrollo y aneuploidías dependientes fundamentalmente de la edad materna. También se hace mención a algunos aspectos del envejecimiento uterino y sus consecuencias en el desarrollo y función placentaria. El enfoque se centra fundamentalmente en la mujer, pero incluye aspectos de la contribución masculina a esta temática.

This article analyzes the effects of the postponement of maternity in three areas: i) demographic, ii) clinical and perinatological and iii) biological. Of course, the existing demographic literature comes primarily from well-developed countries, but an effort has been made to collect as much data from developing countries. The situation in Europe, the U.S. and Latin America is analyzed to end this section with the specific reality in Chile. From the clinical point of view, special interest is placed on changes in the probability of pregnancy by cycle (defined as fecundability) and fertility in general. In the perinatological aspects, the increased frequency of early fetal death (spontaneous abortion) and stillbirth is emphasized, with special mention of some pathologies (frequency of Down syndrome and others). It is also stressed the significant higher frequency of low and very low birth weight, the need newborn hospitalization (perinatal morbidity), as well as the effects on neonatal mortality. Biologically, the postponement of maternity has its correlation in the loss of ovarian reserve and the decrease in oocyte quality that involves an increased incidence of fertilization failure and embryos with low potential for development and aneuploidies, mainly dependent on maternal age. Some aspects of uterine aging and its consequences on placental development and function are also mentioned. The discussion is mainly focused on women, but includes some aspects of the male contribution to this issue

Human endometrial stromal cells inhibit the pro-angiogenic stimulus of hCG in vitro.

During embryo implantation, endometrial angiogenesis is regulated by signals originating from the endometrium itself and the developing embryo. It has been suggested that hCG may play a pro-angiogenic role; therefore, we sought to understand its regulatory role in blood vessel formation in human endometrium using in vivo and in vitro models. In the in vivo model, we screened 16 angiogenesis-related transcripts in the endometrium upon intrauterine administration of hCG. Oocyte donors were recruited and during their controlled ovarian stimulation cycle received a single dose of hCG or vehicle on the day of oocyte pick up during a cycle of ovarian stimulation. One hour before obtaining an endometrial sample, women received an intrauterine administration of vehicle or hCG (500, 1500 and 5000 IU). Transcript and protein analysis showed that MMP3 and VEGFA increased, whereas TIMP1 decreased. The in vitro analysis studied the angiogenic potential of conditioned medium (CM) from primary cultures of human endometrial stromal cells (ESC) stimulated with hCG. Using a 2D and 3D in vitro angiogenesis assays, our results indicate that CM from ESC almost completely inhibits the capillary-like structure formation in endothelial cells, overriding the pro-angiogenic effect of hCG; and this inhibition due to secreted factors present in CM specifically reduced the migration potential of endothelial cells. In conclusion, the endometrial stromal milieu seems to modulate the direct pro-angiogenic effects of hCG on endothelial cells during embryo implantation.

Androgens Profile in Blood Serum and Follicular Fluid of Women With Poor Ovarian Response During Controlled Ovarian Stimulation Reveals Differences Amongst POSEIDON Stratification Groups: A Pilot Study.

Patients with poor ovarian response (POR) to exogenous gonadotropins stimulation for assisted reproductive technology (ART) have decreased circulating androgens during spontaneous cycles. The Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) is a 4-tier stratification of women with POR to controlled ovarian stimulation (COH) based on age and biomarkers of ovarian reserve has been proposed to maximize the clinical management of this group for ART. The aim of the present study was to characterize the levels of androgens during COH in follicular fluid (FF) and serum in POSEIDON subgroups and compared them with women of normal ovarian response. Sixty nine consecutive patients undergoing ART were included and testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), estradiol, sex hormone-binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1) were measured in serum and FF collected at the time of oocyte pick-up. The number of retrieved oocytes was registered for each patient for their allocation to the respective POSEIDON subgroup. The control group comprised 19 women and the POSEIDON group 1 (age < 35, normal ovarian reserve biomarkers) n = 14, group 2 (age ≥ 35, normal ovarian reserve biomarkers) n = 8, group 3 (age < 35, poor ovarian reserve biomarkers) n = 6 and group 4 (age ≥ 35, poor ovarian reserve biomarkers) n = 22. Serum levels of total testosterone, androstenedione and DHEA-S were not different in group 1 vs. control but significantly decreased in group 3 vs. control. DHEA-S in FF was also significantly decreased in group 3 vs. control. In addition, serum testosterone was decreased in groups 2 and 4 vs. control; and serum androstenedione and estradiol were reduced in group 4 vs. control. No differences were observed for estradiol, SHBG and IGF-1 in FF. Finally, a high correlation between serum and FF DHEA-S was observed when data from samples of all groups were pooled. Group 1 did not show hypoandrogenemia however group 3 had low levels of all measured androgens in serum and DHEA-S in FF. Such differences might help to better characterize and/or improve the clinical management of women with POR according to their respective POSEIDON stratification.

[Delayed child bearing in a Chilean public hospital]. / Niveles socioeconómicos bajo y medio bajo comienzan a postergar la maternidad en Santiago de Chile.

BACKGROUND: Postponement of motherhood is one of the most striking sociodemographic changes of modernity. AIM: To evaluate the age of primiparous women giving birth at a public hospital in Santiago, Chile. MATERIAL AND METHODS: Retrospective study, assessing the age and nationality of all women whose delivery occurred between 2009 and 2017 in a single hospital. RESULTS: A total of 49,254 deliveries were registered: 43% were in primiparous women (73% Chilean and 27% foreign women). The proportion of foreign women increased from 12% in 2009 to more than 60% of total deliveries in 2017. Four percent of primiparous women were aged over 35 years of age and there was a steady increase in the age increase of primiparous women in the nine years of study. There was a higher proportion of normal-weight newborns among foreign women compared to their Chilean counterparts (86 and 81% respectively). CONCLUSIONS: In this sample of women attended at a public hospital, a steady increase in the age at first delivery was noted in a period of nine years. There was also a constant increase in the proportion of foreign women giving birth.

Niveles socioeconómicos bajo y medio bajo comienzan a postergar la maternidad en Santiago de Chile / Delayed child bearing in a Chilean public hospital

Background: Postponement of motherhood is one of the most striking sociodemographic changes of modernity. Aim: To evaluate the age of primiparous women giving birth at a public hospital in Santiago, Chile. Material and Methods: Retrospective study, assessing the age and nationality of all women whose delivery occurred between 2009 and 2017 in a single hospital. Results: A total of 49,254 deliveries were registered: 43% were in primiparous women (73% Chilean and 27% foreign women). The proportion of foreign women increased from 12% in 2009 to more than 60% of total deliveries in 2017. Four percent of primiparous women were aged over 35 years of age and there was a steady increase in the age increase of primiparous women in the nine years of study. There was a higher proportion of normal-weight newborns among foreign women compared to their Chilean counterparts (86 and 81% respectively). Conclusions: In this sample of women attended at a public hospital, a steady increase in the age at first delivery was noted in a period of nine years. There was also a constant increase in the proportion of foreign women giving birth.

An increase in IL-1ß concentrations in embryo culture-conditioned media obtained by in vitro fertilization on day 3 is related to successful implantation.

PURPOSE: This study aimed to evaluate interleukin (IL)-1ß concentrations in maternal serum and in embryo-cultured conditioned media and to correlate these findings with success of implantation. METHODS: A total of 70 infertile women who underwent in vitro fertilization treatment were studied. IL-1ß concentrations were quantified in maternal serum and in embryo culture-conditioned media on days 1 and 3. The findings were compared between those who achieved pregnancy and those who did not. RESULTS: No significant differences were found in IL-1ß serum concentrations between the groups. IL-1ß was not detected in day 1 culture-conditioned medium. On day 3, IL-1ß was quantified in 27 patients, and IL-1ß concentrations were significantly higher in women who achieved pregnancy than in those who did not (p < 0.001). CONCLUSIONS: High IL-1ß concentrations in day 3 culture-conditioned medium in patients who achieve pregnancy after in vitro fertilization treatment indicate a possible role of embryonic IL-1ß in the implantation process.