Complicaciones obstétricas y perinatales en mujeres infértiles que se embarazan / Obstetric and perinatal complications in infertile women who become pregnant

Las pacientes infértiles tienen un riesgo aumentado de resultados obstétricos y perinatales adversos que dependen de los factores de infertilidad subyacentes previos y de factores inherentes a los tratamientos recibidos para lograr el embarazo. La edad materna, las patologías previas ginecológicas, hormonales, endocrinológicas, metabólicas y anatomo funcionales son reconocidas como factores de riesgo para resultados adversos obstétricos y perinatales. Los tratamientos como la hiperestimulación ovárica y los tratamientos de reproducción asistida condicionan riesgos adicionales, especialmente por el aumento de embarazos múltiples que se generan con estas terapias. El aumento de la edad materna de pacientes tratadas por infertilidad y la necesidad creciente de tratamientos de reproducción asistida determinan probablemente, un mayor riesgo futuro de complicaciones obstétricas y perinatales. Muchos de estos factores de riesgo pueden ser modificados y manejados antes de iniciar los tratamientos con la finalidad de mejorar el pronóstico para la madre y el recién nacido. La consideración de estos factores de riesgo y sus consecuencias en el embarazo son parte esencial del consejo reproductivo que debiera recibir toda paciente que se somete a tratamientos por infertilidad.El objetivo de esta revisión es mostrar la relación existente entre las pacientes que consultan por infertilidad, los tratamientos usados y los potenciales riesgos obstétricos y perinatales cuando se produce el embarazo.

Infertile patients have an increased risk of adverse obstetric and perinatal outcomes that depend on underlying infertility factors and on those treatments recieved to become pregnant. Maternal age, hormonal, endocrinologial, metabolic and anatomic/functional gynecological diseases are widely recognized risk factors for adverse obstetric and perinatal outcomes. Infertility treatments like controlled ovarian hyperstimulation and assisted reproductive technologies add aditional risks, specially related to multiple pregnancies that are associated to. The higher maternal age of patients seeking for infertility treatment and the increasing need of assisted reproductive technologies probably determines a higher and increasing risk of obstetric and perinatal adverse outcomes. In many cases risk factors can be adequately modified and controlled before treatments are initiated thus improving maternal and neonatal prognosis. This risk factors and their consequences in pregnancy have to be strongly considered in reproductive counselling that should recieve every patient treated for infertility.The aim of this article is to show the relation between infertile patients seeking for treatment and their potential risks of obstetric and perinatal adverse outcomes when they get pregnant.

Resultados maternos y perinatales de los embarazos obtenidos por técnicas de reproducción asistida: revisión de la literatura / Perinatal and maternal outcomes following assisted reproductive technology: a literature review

La utilización de técnicas de reproducción asistida (TRA) ha aumentado en todo el mundo, incluyendo procedimientos como la donación de gametos, la subrogación y el diagnóstico genético preimplantacional. Creciente evidencia confirma que los embarazos de pacientes sometidas a estos tratamientos tienen un mayor riesgo de complicaciones perinatales. No queda claro si la causa de estos hallazgos se debe a la infertilidad subyacente o los tratamientos en sí. Esta revisión tiene como objetivo resumir la evidencia actual acerca de los efectos sobre los resultados maternos y perinatales tanto de los diferentes procedimientos propios de la fecundación in vitro como de algunos tipos de TRA especiales.

The use of assisted reproduction techniques (ART) has increased worldwide, including procedures such as gamete donation, subrogation and preimplantation genetic diagnosis. Growing evidence confirms that pregnancies following these treatments have an increased risk of adverse perinatal outcomes. It is not clear whether the cause of these findings is due to the underlying infertility or the treatments themselves. This review aims to summarize the current evidence regarding the effects of both the different ART procedures and some special types of ART on maternal and perinatal outcomes.

Factores clínico-terapéuticos y su relación con la calidad embrionaria en pacientes sometidas a fertilización in vitro / Clinical and therapeutic factors and their relationship with the embryo quality in patients subjected to in vitro fertilization

Introducción: la fertilización in vitro con transferencia embrionaria es el tratamiento de infertilidad más empleado en las técnicas de reproducción asistida. Objetivo: identificar factores clínicos-terapéuticos que inciden en la calidad de los embriones obtenidos por fertilización in vitro, en pacientes infértiles en las que se emplea esta técnica. Métodos: se realizó un estudio longitudinal de corte retrospectivo, en el cual se precisó la influencia de factores clínicos-terapéuticos, tales como, edad materna, dosificación de la hormona folículo estimulante en ciclo previo, número de ovocitos aspirados en el ciclo de fertilización in vitro, análogo de la hormona liberadora de gondadotropinas utilizado y la causa de infertilidad, en la calidad de los embriones cultivados. Resultados: de 419 parejas estudiadas, se obtuvieron tríos embrionarios de buena calidad en el 60,86 por ciento. Hubo diferencias estadísticamente significativas entre las pacientes con buena y mala calidad embrionaria, en cuanto a la edad (p= 0,029), el número de ovocitos aspirados (p< 0,0001) y la causa de infertilidad (p= 0,002). En el análisis multivariado, la causa inexplicable de infertilidad (odds ratio: 0,13 [95 por ciento IC: 0,036-0,49]; p= 0,002) y la edad (odds ratio: 0,96 [95 por ciento IC: 0,81-0,99]; p= 0,042) se asociaron a la abtención de embriones de mala calidad, mientras que el mayor número de ovocitos aspirados se asoció con la obtención de embriones de buena calidad (odds ratio: 1,08 [95 por ciento IC: 1,03-1,13]; p= 0,002). Conclusiones: la obtención de embriones de buena calidad se favorece de un mayor número de ovocitos aspirados; mientras que la infertilidad de causa inexplicable, y el aumento de la edad, la disminuyen(AU)

ntroduction: in vitro fertilization with embryo transfer is the most used infertility treatment in the assisted reproductive techniques. Objective: to identify the clinical and therapeutic factors affecting the quality of embryos obtained from in vitro fertilization in infertile patients undergoing this technique. Methods: a retrospective longitudinal study was conducted to determine the influence of clinical and therapeutic factors such as maternal age, dosage of follicle-stimulating hormone in previous cycle, number of aspired oocytes in the in vitro fertilization cycle, the analogue of the gonadotropin-releasing hormone used and the cause of infertility on the quality of cultured embryos. Results: of 419 studied couples, good quality embryo trios were obtained in 60.86 percent of the sample. There were statistically significant differences between the patients with good and with bad embryo quality in terms of age (p= 0.029), number of aspired ovocytes (p< 0.0001) and cause of infertility (p< 0.002). In multivariate analysis, the unknown cause of infertility (odds ratio: 0.13 [95 percent CI: 0.036-0.49]; p= 0.002) and the age (odds ratio: 0.96 [95 percent CI: 0.81-0.99]; p= 0.042) were associated to obtaining low quality embryos whereas the highest number of aspired ovocytes was associated to good quality embryos (odds ratio: 1.08 [95 percent CI: 1.03-1.13]; p= 0.002). Conclusions: a higher number of aspired oocytes encourages obtaining good quality embryos whereas infertility of unknown cause and older age reduce it(AU)

Evaluation of a father and son with atypical chronic myeloid leukemia with SETBP1 mutations and a review of the literature

We report the case of a father and son diagnosed with atypical chronic myeloid leukemia (aCML). Both patients harbored SETBP1 mutations, which are present in 24.3% of aCML patients. Moreover, both shared the variant encoding p.Pro737His, but the aCML severity was greater in the son because of the presence of two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations. SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient's prognosis.

Do induced twin pregnancies influence the obstetric and neonatal results of multiple births born before 32 weeks? Comparison to spontaneous gestation / Gestações gemelares induzidas modificam o resultado obstétrico e perinatal de partos antes da 32ª semana? Comparação com gestações espontâneas

PURPOSE: To compare obstetric outcomes of induced preterm twin births (under 32 weeks gestation) with those spontaneously conceived. METHODS: Prospective study of twin pregnancies (25 induced and 157 spontaneously conceived) developed over a period of 16 years in a tertiary obstetric center. Demographic factors, obstetric complications, gestational age at delivery, mode of delivery, birth weight and immediate newborn outcome were compared. RESULTS: The analysis of obstetrical complications concerning urinary or other infections, hypertensive disorders of pregnancy, gestational diabetes, fetal malformations, intrauterine fetal death, intrauterine growth restriction and intrauterine discordant growth reveal no significant statistical differences between the two groups. First trimester bleeding was higher in the induced group (24 versus 8.3%, p=0.029). The cesarean delivery rate was 52.2% in spontaneous gestations and 64% in induced gestations. Gestational age at delivery, birth weight, Apgar scores at first and fifth minutes, admissions to Neonatal Intensive Care Unit and puerperal complications show no statistically significant differences between the two groups. These results were independent of chorionicity and induction method. CONCLUSION: The mode of conception did not influence obstetric and neonatal outcomes. Although induced pregnancies have higher risk of first trimester bleeding, significant differences were not observed regarding other obstetric and puerperal complications and neonatal results. .

OBJETIVO: Comparar os resultados obstétricos de gestações gemelares induzidas com as concebidas espontaneamente, em partos ocorridos antes da 32ª semana de idade gestacional. MÉTODOS: Estudo prospectivo de gestações gemelares (25 induzidas e 157 concebidas espontaneamente) desenvolvido durante um período de 16 anos num centro terciário de Obstetrícia. Foram comparados fatores demográficos, complicações obstétricas, idade gestacional no parto, tipo de parto, peso ao nascer e o outcome imediato do recém-nascido. RESULTADOS: A análise das seguintes complicações obstétricas: infecções urinárias ou outras, distúrbios hipertensivos da gravidez, diabetes gestacional, malformações fetais, morte fetal intrauterina, restrição de crescimento intrauterino e crescimento intrauterino discordante não revelou diferenças estatísticas significativas entre os dois grupos. No grupo das gestações induzidas, observou-se maior taxa de metrorragias do 1º trimestre (24 versus 8,3%, p=0,029). A taxa de cesariana foi de 52,2% nas gestações espontâneas e 64% nas gestações induzidas. Idade gestacional no parto, peso ao nascer, índice de Apgar no primeiro e quinto minutos, internamento em unidade de cuidados intensivos neonatal e complicações puerperais não apresentam diferenças estatisticamente significantes entre os dois grupos. Esses resultados foram independentes do tipo de placentação e método de indução. CONCLUSÃO: O modo de concepção não influenciou os resultados obstétricos e neonatais. Embora as gestações induzidas tenham maior risco de metrorragias do primeiro trimestre, não foram observadas diferenças significativas em relação a outras complicações obstétricas, complicações puerperais e em relação aos resultados neonatais. .

Riesgos y complicaciones de los tratamientos de infertilidad / Risks and complications of infertility treatments

El desarrollo y uso masivo de técnicas de fecundación asistida desde hace 30 años ha permitido el nacimiento de más de 3 millones de niños en el mundo; sin embargo, estos procedimientos no están exentos de riesgos. La complicación más frecuente es el embarazo múltiple determinado por el desarrollo de múltiples folículos en la inseminación intrauterina y la transferencia de 2 ó más embriones en la fecundación in-vitro. El síndrome de hiperestimulación ovárica constituye una complicación menos frecuente, pero potencialmente grave para la cual detallamos las estrategias de prevención y manejo clínico. Se discuten además las complicaciones derivadas de la aspiración folicular tales como hemorragia e infección entre otras.

The widespread use of fertility treatments such as in-vitro fertilization has determined the birth of more than 3 million babies worldwide, however, these procedures can derive into medical complications. The most frequent complication of assisted reproductive techniques is multiple pregnancy. Single embryo transfer has been avdocated as the best strategy to prevent this complication. Ovarian hyperstimulation syndrome constitutes a life threathening complication of ovarian stimulation. Detailed information on prevention and treatment strategies are given. Other complications after oocyte retrieval such as bleeding and infection are also discussed.

Ovarian abscess as a complication of assisted reproduction techniques: a case report

AMP makes true great strides these last decades. Logically some complications were noticed even due to ovarian puncture such as hemorrhage, perforation or infection. The aim of this report is to try, through a review of literature, to draw the attention of physicians to a rare entity, ovarian abscess after follicle aspiration for in-vitro fertilization, and to means of prevention. We report a 38-year-old woman who was compolaining from lower abdominal pain located in the left iliac fossa one month after failed IVF trial. The pain was associated with fever and vomiting. The patient's past medical history involves 2 myomectomys [2003-2007]. On admission, her temperature was 38.9°C and her blood pressure was 90/60 mm Hg. Physical examination found nondistended abdomen. Tenderness to deep palpation in the left lower quadrant, without peritoneal signs, was detected. No masses were palpated. Mild tenderness in the left cul-de-sac was found. A full blood count showed a white cell count of 17,500 cells/mm3 with 84.5% polymorph nuclear cells, CRP 173 mg/dl. Pelvic ultrasound shows a left latero uterine mass; right ovary and the uterus are unremarkable; there was no free abdominal fluid. The laparotomy was performed 24 hours later and a left ovarian abscess was found. The treatment was conservative. Antibiotics were associated during 15 days. The clinical evolution was satisfying. The ovarian puncture might be technically difficult, incomplete, and even impossible which exposes to a greater infection risk. An ultrasound evaluation of ovarian accessibility is necessary before starting an IVF attempt, especially in case of overweight or history of abdominal or pelvic surgery, endometriosis tubal abnormalities or myomas. The treatment is based on surgery and antibiotics

Complicações maternas e ocorrências neonatais associadas às gestações múltiplas resultantes de técnicas de reprodução assistida / Maternal complications and neonatal events associated to multiple pregnancies resulting from assisted reproduction techniques / Complicaciones maternas e eventos neonatales asociados con gestaciones múltiples resultantes de técnicas de reproducción asistida

A gestação múltipla é a mais freqüente e a mais séria complicação iatrogênica das técnicas de reprodução assistida. O objetivo do estudo foi conhecer as complicações maternas e as ocorrências neonatais associadas às gestações múltiplas resultantes de reprodução assistida em um centro de referência na área de reprodução assistida. Trata-se de uma pesquisa observacional, transversal, descritiva e retrospectiva que foi realizada no Hospital e Maternidade Santa Joana, centro de referência na área de reprodução humana localizado no município de São Paulo, Brasil. A população estudada foi constituída por 131 prontuários de gestantes internadas com patologias clínicas e trabalho de parto, advindas de gestações múltiplas resultantes de técnicas de reprodução assistida. As complicações maternas predominantes foram: o trabalho de parto prematuro (65,5%), a amniorrexe prematura (42%). As ocorrências neonatais mais freqüentes foram as doenças respiratórias (65,1%), a icterícia (38,4%), os distúrbios metabólicos (13%) e as doenças neurológicas (9%).

Multiple pregnancy is the most frequent and serious iatrogenic complication of the assisted reproduction techniques. The purpose of this study was to know the maternal complications and neonatal events associated to multiple pregnancies, resulting from assisted reproduction in a reference center in the field of assisted reproduction. This was an observational, cross-section, descriptive and retrospective study performed at Hospital e Maternidade Santa Joana, a reference center in the area of human reproduction in the city of São Paulo, Brazil. The studied population consisted of 131 medical records of pregnant women admitted with clinical pathologies and in labor, resulting from multiple pregnancies resulting from assisted reproduction techniques. The predominant maternal complications were: premature labor (65.5%) and premature amniorrhexis (42%), The most frequent neonatal occurrences were respiratory diseases (65.1%), jaundice (38.4%), metabolic disorders (13%) and neurological diseases (9%).

La gestación múltiple es la más frecuente y corresponde a la más seria complicación iatrogénica de las técnicas de reproducción asistida. El objetivo del estudio fue conocer las complicaciones maternas y los eventos neonatales asociados a las gestaciones múltiples resultantes de la reproducción asistida en un centro de referencia en el área de reproducción asistida. Se trata de una investigación observacional, transversal, descriptiva y retrospectiva que fue realizada en el Hospital y Maternidad Santa Joana, centro de referencia en el área de reproducción humana, localizado en el municipio de São Paulo, Brasil. La población estudiada fue constituida por 131 registros de gestantes internadas con patologías clínicas y trabajo de parto, provenientes de gestaciones múltiplas resultantes de técnicas de reproducción asistida. Las complicaciones maternas predominantes fueron: el trabajo de parto prematuro (65,5%) y la ruptura prematura del saco amniótico (42%). Los eventos neonatales más frecuentes fueron las enfermedades respiratorias (65,1%), la ictericia (38,4%), los disturbios metabólicos (13%) y las enfermedades neurológicas (9%).

Perinatal outcome after multifetal pregnancy reduction.

OBJECTIVE: To assess multifetal pregnancy reduction in Indian context. METHODS: It is a retrospective descriptive study. Perinatal outcome of 92 multifetal pregnancies were retrieved from a well maintained database. Fetal reductions were carried out using standard protocol. RESULTS: There were 92 pregnancies referred for fetal reduction during the study period. Out of 92, twelve pregnancies (20.3%) had fetal or neonatal losses; of which complete pregnancy loss rate was 8.5% and partial pregnancy loss rate was 11.8%. Twenty one (35.6%) pregnancies had premature deliveries. The median birth weight was 2100 grams. Four babies were born alive with congenital anomalies. CONCLUSION: Our study showed the median birth weight, rates of pregnancy loss and prematurity after the fetal reduction procedure was comparable with other studies. However, it must be noted that the rate of loss to follow up was higher in our study.

Heterotopic pregnancy: a case report

Heterotopic pregnancy is a catastrophic form of ectopic pregnancy and its incidence is still low but it is increasing, mainly secondary to the increase in assisted reproductive technology procedures. The definition of heterotopic pregnancy is the simultaneous development of an intrauterine pregnancy and an extrauterine one. We report a case of 33-year-old woman with intrauterine viable fetus and right tubal heterotopic pregnancy

Daño al ADN espermático: aspectos clínicos y biológicos / Sperm DNA damage: clinical and biological aspects

Cada vez más, la integridad del ADN espermático es reconocida como una medida independiente de su calidad. La integridad del ADN del espermatozoide es de vital importancia en el inicio y mantenimiento de un embarazo a término tanto in vivo como in vitro. El estudio rutinario del semen no identifica defectos en la arquitectura de la cromatina espermática. La intención de esta revisión es hacer énfasis en la información pertinente al origen, las causas y algunos métodos de estudio del daño al ADN espermático, especialmente su significación clínica y su relación con la infertilidad masculina. La evaluación de la integridad del ADN en el espermatozoide, además del estudio de los parámetros sistemáticos seminales, podría aportar una información adicional acerca de la calidad del espermatozoide. Esto podría aliviar los problemas sociales y emocionales asociados con los intentos fallidos en las técnicas de reproducción asistida(AU)

The DNA integrity is increasingly recognized as a measure independent of its quality. The sperm DNA integrity is very important in the beginning and maintenance of a pregnancy at term, both in vivo and in vitro. The routine study of semen does not identify defects in the architecture of the spermatic chromatin. This review is aimed at making emphasis on the information related to the origin, causes and some methods used to study the sperm DNA damage, specially its clinical significance and its connection with male infertility. The evaluation of the sperm DNA integrity, besides studying the systematic seminal parameters, may give additional information about the spermatozoid quality. This could help to alleviate the social and emotional problems associated with the failed attempts in the assisted reproductive techniques(AU)

Utilização de técnicas de reprodução assistida e resultados perinatais / Use of assisted reproduction technologies and perinatal outcome

Nos ultimos anos, cada vez mais se tem difundido as técnicas de reprodução assistida e seu uso. A sua relação com malformações fetais e outras alterações em crianças geradas por estas técnicas têm sido objeto de grande discussão. Através da análise da literatura dos últimos 15 anos foi possível observar que os estudos parecem demonstrar um aumento da frequência de malformações urinárias em meninos concebidos por TRA e novos pontos de discussão têm sido levantados como risco de neoplasias, defeitos de imprinting gênico, alterações do desenvolvimento neuropsicomotor e até questionamentos com relação à fertilidade futura destas crianças. São necessários ainda novos estudos abrangendo casuísticas mais extensas e um seguimento a médio e longo prazo destas crianças.

El riesgo de malformaciones congénitas y defectos de la programación genómica, en relación con las técnicas de reproducción asistida y la clonación / The risk of congenital malformations and genomic imprinting defects in assisted reproductive technologies and nuclear transfer cloning

Recent studies show that assisted reproductive technologies (ART), whether in vitro fertilization (IVF) or intra-cytoplasmatic sperm injection (ICSI) or applied to cloning by somatic cell nuclear transfer (SCNT) are associated to a higher risk of congenital malformations and errors in deprogramming, maintenance or reprogramming genomic imprinting in humans and animals. IVF and ICSI are also associated to an increased admission to neonatal intensive care units and more need for health care resources in infancy. A mutagenic effect of a chemical used in SCNT has been reported and gene depression was found in bovine embryos obtained by IVF or SCNT. The causes of these anomalies could be pathological conditions for which ART is applied, a direct effect of technologies on the zygotes or embryos, avoidance for zygotes or embryos of the oviduct path that is needed to elicit necessary immunity or genomic programming processes, or adaptive selective steps acquired during thousands of millions of generations in evolution. The knowledge of evolution is emphasized as essential in the scientific ethical analysis.

[ role of intravenous albumin in the prevention of severe ovarian hyperstimulation syndrome in ART cycles]

The objective of this study was to evaluate the effect of ablumin on inhibition of severe ovarian hyperstimulation syndrome [OHSS] in women at high risk. A prospective, interventive and randomized study was planned and performed at the IVF department of the Royan Research Center. Ninety high risk patients from moderate to serere OHSS who were undergoing IVF ICSI cycles, were divided in two groups. 57 patients in the study group and 33 in the control group. At the time of oocyte recovery, 50gr human albumin in 500 ml of normal saline [N.S] was injected to the study group. The control group only received 500 ml N.S. All patients in study and control groups were matched for age, number of oocytes, level of Estradiol at the time of hCG injection, duration of Follicular phase, amount of hMG used and the number of the transferred embryos. Of the 57 patients in the study group, one had OHSS, while in the control group, 4 OHSS patient was found in 33 patients [1/8% versus 2%, p<0.05]. We conclude that prophylactic infusion of human serum albumin can reduce or mitigate severe OHSS in patients at high risk