Outcome of prelabor rupture of membranes before or at the limit of viability: systematic review and meta-analysis.

OBJECTIVE: Counseling of pregnancies complicated by pre- and periviable premature rupture of membranes to reach shared decision-making is challenging, and the current limited evidence hampers the robustness of the information provided. This study aimed to elucidate the rate of obstetrical and neonatal outcomes after expectant management for premature rupture of membranes occurring before or at the limit of viability. DATA SOURCES: Medline, Embase, CINAHL, and Web of Science databases were searched electronically up to September 2023. STUDY ELIGIBILITY CRITERIA: Our study included both prospective and retrospective studies of singleton pregnancies with premature rupture of membranes before and at the limit of viability (ie, occurring between 14 0/7 and 24 6/7 weeks of gestation). METHODS: Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. Moreover, our study used meta-analyses of proportions to combine data and reported pooled proportions. Given the clinical heterogeneity, a random-effects model was used to compute the pooled data analyses. This study was registered with the International Prospective Register of Systematic Reviews database (registration number: CRD42022368029). RESULTS: The pooled proportion of termination of pregnancy was 32.3%. After the exclusion of cases of termination of pregnancy, the rate of spontaneous miscarriage or fetal demise was 20.1%, whereas the rate of live birth was 65.9%. The mean gestational age at delivery among the live-born cases was 27.3 weeks, and the mean latency between premature rupture of membranes and delivery was 39.4 days. The pooled proportion of cesarean deliveries was 47.9% of the live-born cases. Oligohydramnios occurred in 47.1% of cases. Chorioamnionitis occurred in 33.4% of cases, endometritis in 7.0%, placental abruption in 9.2%, and postpartum hemorrhage in 5.3%. Hysterectomy was necessary in 1.2% of cases. Maternal sepsis occurred in 1.5% of cases, whereas no maternal death was reported in the included studies. When focusing on neonatal outcomes, the mean birthweight was 1022.8 g in live-born cases. The neonatal intensive care unit admission rate was 86.3%, respiratory distress syndrome was diagnosed in 66.5% of cases, pulmonary hypoplasia or dysplasia was diagnosed in 24.0% of cases, and persistent pulmonary hypertension was diagnosed in 40.9% of cases. Of the surviving neonates, the other neonatal complications included necrotizing enterocolitis in 11.1%, retinopathy of prematurity in 27.1%, and intraventricular hemorrhage in 17.5%. Neonatal sepsis occurred in 30.2% of cases, and the overall neonatal mortality was 23.9%. The long-term follow-up at 2 to 4 years was normal in 74.1% of the available cases. CONCLUSION: Premature rupture of membranes before or at the limit of viability was associated with a great burden of both obstetrical and neonatal complications, with an impaired long-term follow-up at 2 to 4 years in almost 30% of cases, representing a clinical challenge for both counseling and management. Our data are useful when initially approaching such patients to offer the most comprehensive possible scenario on short- and long-term outcomes of this condition and to help parents in shared decision-making. El resumen está disponible en Español al final del artículo.

Delivery management of a complete hydatidiform mole and co-existing viable fetus: A meta-analysis and systematic review.

OBJECTIVE: A twin pregnancy with a complete hydatidiform mole and co-existing viable fetus (CHMCF) is an exceedingly rare obstetric complication with few data related to perinatal treatment. This study determined the optimal timing of pregnancy termination and mode of delivery in women with CHMCF and a viable fetus. METHODS: The articles published involving CHMCF and a viable fetus from 1967 to 31 December 2020 in the PubMed and EMBASE databases were systematically reviewed. Observational cohort studies with three or more cases identified and data on delivery management were selected. The articles were analyzed independently for full text and the data were integrated. The timing of pregnancy termination and mode of delivery were calculated using Review Manager 5.4.1. RESULTS: There were 192 reports involving CHMCF; 209 cases had a viable fetus. According to the inclusion criteria, there were 6 case series, including 72 cases that were eligible for the analysis. The average rate of live births was 34.4%. The average duration of pregnancy was 34 weeks, ranging from 25 to 41 weeks. From 2000-2017 the live birth rate was increased year-after-year. Specifically, the live birth rate was16.7% in 2000, 33.3% in 2012, and 50% in 2017. Fifty-two cases (72.2%) had cesarean sections and 20 cases (27.8%) had vaginal deliveries. The incidence of gestational trophoblastic neoplasia was not significantly different between the two modes of delivery. CONCLUSIONS: Ideally, a twin pregnancy with a complete hydatidiform mole co-existing with a viable fetus is managed by an obstetrician, pediatrician, and oncologist. Appropriate timing of pregnancy termination and mode of delivery are related to the pregnancy outcome.

Viability and thresholds for treatment of extremely preterm infants: survey of UK neonatal professionals.

BACKGROUND: Decisions about treatments for extremely preterm infants (EPIs) born in the 'grey zone' of viability can be ethically complex. This 2020 survey aimed to determine views of UK neonatal staff about thresholds for treatment of EPIs given a recently revised national Framework for Practice from the British Association of Perinatal Medicine. METHODS: The online survey requested participants indicate the lowest gestation at which they would be willing to offer active treatment and the highest gestation at which they would withhold active treatment of an EPI at parental request (their lower and upper thresholds). Relative risks were used to compare respondents' views based on profession and neonatal unit designation. Further questions explored respondents' conceptual understanding of viability. RESULTS: 336 respondents included 167 consultants, 127 registrars/fellows and 42 advanced neonatal nurse practitioners (ANNPs). Respondents reported a median grey zone for neonatal resuscitation between 22+1 and 24+0 weeks' gestation. Registrars/fellows were more likely to select a lower threshold at 22+0 weeks compared with consultants (Relative Risk (RR)=1.37 (95% CI 1.07 to 1.74)) and ANNPs (RR=2.68 (95% CI 1.42 to 5.06)). Those working in neonatal intensive care units compared with other units were also more likely to offer active treatment at 22+0 weeks (RR=1.86 (95% CI 1.18 to 2.94)). Most participants understood a fetus/newborn to be 'viable' if it was possible to survive, regardless of disability, with medical interventions accessible to the treating team. CONCLUSION: Compared with previous studies, we found a shift in the reported lower threshold for resuscitation in the UK, with greater acceptance of active treatment for infants <23 weeks' gestation.

Simple trachelectomy with pelvic lymphadenectomy as a viable treatment option in pregnant patients with stage IB1 (≥2 cm) cervical cancer: Bridging the gap to fetal viability.

OBJECTIVE: Cervical cancer is the most common gynecologic cancer in pregnancy. This study aims to evaluate simple trachelectomy and pelvic lymphadenectomy in patients with stage IB1 (≥2 cm) cervical cancer wishing to maintain their pregnancy. METHODS: We included patients with stage IB1 (≥2 cm) cervical cancer who underwent simple trachelectomy and minimally invasive pelvic lymphadenectomy during pregnancy from January 2004 to August 2016. Data analysis included demographics, perioperative, obstetrics, and oncologic outcomes. RESULTS: A total of 5 patients were included. Median age was 30 years (range; 26-38). Median gestational age (GA) at diagnosis was 12 weeks (range; 7-18) and at treatment intervention 16.5 weeks (range; 12-19). Histologic subtypes included: adenocarcinoma (3 patients) and squamous cell carcinoma (2 patients). Median tumor size by clinical exam was 27 mm (range; 20-40), grade 2 (range; 2-3) and depth of invasion 10 mm (range; 1.5-12). All patients underwent laparoscopic (1) or robotic (4) pelvic lymphadenectomy followed by vaginal simple trachelectomy. Median operative time was 193 min (range; 155-259), estimated blood loss 100 ml (range; 50-550) and length of stay 2 days (range; 1-3). There were no intraoperative or postoperative complications (<30 days). Median number of lymph nodes removed was 14 (range; 5-15). One patient had bilateral microscopic positive nodes. The median gestational age at delivery was 39 weeks (range; 28-40.6). After median follow-up of 75 months (range; 18-168), all patients are alive without disease. CONCLUSION: Simple trachelectomy with pelvic lymph node dissection may be a safe option in pregnant patients with stage IB1 (>2 cm) cervical cancer wishing to maintain their pregnancy.

DNA damage in Wistar Kyoto rats exercised during pregnancy

Abstract Purpose: To evaluate DNA damage levels in pregnant rats undergoing a treadmill exercise program. Methods: Wistar Kyoto rats were allocated into two groups (n= 5 animals/group): non-exercise and exercise. The pregnant rats were underwent an exercise protocol on a treadmill throughout pregnancy. Exercise intensity was set at 50% of maximal capacity during maximal exercise testing performed before mating. Body weight, blood pressure and glucose levels, and triglyceride concentration were measured during pregnancy. At day 10 post-natal, the animals were euthanized and maternal blood samples were collected for DNA damage. Results: Blood pressure and glucose levels and biochemical measurements showed no significant differences. Increased DNA damage levels were found in exercise group compared to those of non-exercise group (p<0.05). Conclusion: The exercise intensity protocol used in the study might have been exhaustive leading to maternal increased DNA damage levels, demonstrating the relevance of an adequate protocol of physical exercise.

Association of gestational age with the option of pregnancy termination for fetal abnormalities incompatible with neonatal survival.

OBJECTIVE:: To identify the profile of women seen in a Fetal Medicine unit, diagnosed with fetal abnormality incompatible with neonatal survival in their current pregnancy, and to check the association of gestational age upon diagnosis with the option of pregnancy termination. METHODS:: This is a retrospective cohort study carried out in the Fetal Medicine Outpatients Clinic of a university hospital, in the city of São Paulo (SP), Brazil, using medical records of pregnant women with fetus presenting abnormalities incompatible with neonatal survival. The sample comprised 94 medical records. The Statistical Package for the Social Sciences (SPSS), version 19, was used for the data statistical analysis. RESULTS:: The population of the study included young adult women, who had complete or incomplete high school education, employed, with family income of one to three minimum wages, single, nonsmokers, who did not drink alcoholic beverages or used illicit drugs. Women with more advanced gestational age upon fetal diagnosis (p=0.0066) and/or upon admission to the specialized unit (p=0.0018) presented a lower percentage of termination of pregnancy. CONCLUSION:: Due to characteristics different from those classically considered as of high gestational risk, these women might not be easily identified during the classification of gestational risk, what may contribute to a late diagnosis of fetal diseases. Early diagnosis enables access to specialized multiprofessional care in the proper time for couple's counseling on the possibility of requesting legal authorization for pregnancy termination. OBJETIVO:: Identificar o perfil de mulheres atendidas em um serviço de Medicina Fetal, que receberam diagnóstico de anomalia fetal incompatível com a sobrevida neonatal na gestação atual, e verificar a associação da idade gestacional no diagnóstico com a opção pela interrupção da gravidez. MÉTODOS:: Trata-se de um estudo de coorte retrospectivo, realizado no ambulatório de Medicina Fetal de um hospital universitário da cidade de São Paulo (SP), com prontuários de mulheres com fetos portadores de anomalias incompatíveis com a sobrevida neonatal na gestação atual. A amostra constituiu-se de 94 prontuários. Para análise estatística dos dados, utilizou-se o programa Statistical Package for the Social Sciences (SPSS), versão 19. RESULTADOS:: A população foi de mulheres adultas jovens, com escolaridade compatível com o Ensino Médio completo/incompleto, empregadas, com renda familiar entre um e três salários mínimo, solteiras, que não faziam uso de tabaco, bebidas alcoólicas ou de drogas ilícitas. Verificou-se que mulheres com maior idade gestacional na ocasião do diagnóstico fetal (p=0,0066) e/ou na chegada ao serviço especializado (p=0,0018) apresentaram menor percentual de interrupção gestacional. CONCLUSÃO:: Por apresentarem características diferentes daquelas classicamente consideradas de alto risco gestacional, é possível que essas mulheres não tenham sido facilmente identificadas durante a classificação de risco gestacional, o que pode ter colaborado para o diagnóstico tardio de patologias fetais. O diagnóstico precoce possibilita acesso à assistência multiprofissional especializada em tempo adequado para aconselhamento do casal sobre a possibilidade de solicitação de autorização judicial para a interrupção gestacional.

Association of gestational age with the option of pregnancy termination for fetal abnormalities incompatible with neonatal survival / Associação da idade gestacional com a opção pela interrupção da gravidez de fetos com anomalias incompatíveis com a sobrevida neonatal

ABSTRACT Objective: To identify the profile of women seen in a Fetal Medicine unit, diagnosed with fetal abnormality incompatible with neonatal survival in their current pregnancy, and to check the association of gestational age upon diagnosis with the option of pregnancy termination. Methods: This is a retrospective cohort study carried out in the Fetal Medicine Outpatients Clinic of a university hospital, in the city of São Paulo (SP), Brazil, using medical records of pregnant women with fetus presenting abnormalities incompatible with neonatal survival. The sample comprised 94 medical records. The Statistical Package for the Social Sciences (SPSS), version 19, was used for the data statistical analysis. Results: The population of the study included young adult women, who had complete or incomplete high school education, employed, with family income of one to three minimum wages, single, nonsmokers, who did not drink alcoholic beverages or used illicit drugs. Women with more advanced gestational age upon fetal diagnosis (p=0.0066) and/or upon admission to the specialized unit (p=0.0018) presented a lower percentage of termination of pregnancy. Conclusion: Due to characteristics different from those classically considered as of high gestational risk, these women might not be easily identified during the classification of gestational risk, what may contribute to a late diagnosis of fetal diseases. Early diagnosis enables access to specialized multiprofessional care in the proper time for couple's counseling on the possibility of requesting legal authorization for pregnancy termination.

RESUMO Objetivo: Identificar o perfil de mulheres atendidas em um serviço de Medicina Fetal, que receberam diagnóstico de anomalia fetal incompatível com a sobrevida neonatal na gestação atual, e verificar a associação da idade gestacional no diagnóstico com a opção pela interrupção da gravidez. Métodos: Trata-se de um estudo de coorte retrospectivo, realizado no ambulatório de Medicina Fetal de um hospital universitário da cidade de São Paulo (SP), com prontuários de mulheres com fetos portadores de anomalias incompatíveis com a sobrevida neonatal na gestação atual. A amostra constituiu-se de 94 prontuários. Para análise estatística dos dados, utilizou-se o programa Statistical Package for the Social Sciences (SPSS), versão 19. Resultados: A população foi de mulheres adultas jovens, com escolaridade compatível com o Ensino Médio completo/incompleto, empregadas, com renda familiar entre um e três salários mínimo, solteiras, que não faziam uso de tabaco, bebidas alcoólicas ou de drogas ilícitas. Verificou-se que mulheres com maior idade gestacional na ocasião do diagnóstico fetal (p=0,0066) e/ou na chegada ao serviço especializado (p=0,0018) apresentaram menor percentual de interrupção gestacional. Conclusão: Por apresentarem características diferentes daquelas classicamente consideradas de alto risco gestacional, é possível que essas mulheres não tenham sido facilmente identificadas durante a classificação de risco gestacional, o que pode ter colaborado para o diagnóstico tardio de patologias fetais. O diagnóstico precoce possibilita acesso à assistência multiprofissional especializada em tempo adequado para aconselhamento do casal sobre a possibilidade de solicitação de autorização judicial para a interrupção gestacional.

Ethical challenges in the new world of maternal-fetal surgery.

This article explores some of the complex ethical challenges that exist in the field of fetal diagnosis and treatment, especially surrounding maternal-fetal surgery. The rise of these new treatments force us to reconsider who or what is the fetus, what are our obligations to the fetus, and what are the limits to those obligations. In addition, we will consider provider and professional biases, disability issues, and how maternal-fetal surgery has, for a select group of women, changed the very experience of motherhood.

The neurological outcomes of surviving twins in severe twin-twin transfusion syndrome treated by fetoscopic laser photocoagulation at a newly established center.

OBJECTIVE: To evaluate the incidence and predictive factors of poor neurological outcome in survivors of twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP). METHODS: Brain magnetic resonance imaging (MRI) and neurodevelopmental assessment were performed at a corrected age of 1 year in survivors of TTTS treated by FLP. Severe neurological abnormality was defined as either the presence of severe clinical neurodevelopmental disability or severe anomalies, visualized on MRI of the brain. RESULT: In a consecutive series of 46 cases treated by FLP, the total survival rate was 66.3%; survival of at least one was 80.4%. Severe neurodevelopment disability was 6.7 % (4/59) and the presence of a severe anomaly on brain imaging was 8.8% (5/57), which combined to a clinical or MRI abnormality rate of 10.5% (6/57). Univariate analysis revealed that early gestational age at delivery was the most significant predictor. However, the multiple logistic regression model did not identify any significant variables. CONCLUSION: In this small series, we determined a rate of clinical neurologic impairment rate at the age of 1 year of 6.7%, which compares to what has been published.

Akt1 and insulin-like growth factor 2 (Igf2) regulate placentation and fetal/postnatal development.

Phenotypic characterization of Akt1 and Igf2 null mice has revealed roles for each in the regulation of placentation, and fetal and postnatal growth. Insulin-like growth factor 2 (IGF2) is encoded by the Igf2 gene and influences cellular function, at least in part, through activation of an intracellular serine/threonine kinase called AKT1. Akt1 and Igf2 null mice were originally characterized on inbred and mixed genetic backgrounds, prohibiting direct comparisons of their phenotypes. The impact of loss of AKT1 or IGF2 on placental, fetal, and postnatal function were examined following transfer of Akt1 and Igf2 null mutations to an outbred CD1 genetic background. Disruption of IGF2 did not affect AKT expression or activation. Both Akt1-/- and Igf2-/- mice exhibited decreased placental weight, fetal weight and viability. Deregulation of placental growth was similar in Akt1 and Igf2 nulls; however, disruption of Igf2 had a more severe impact on prenatal survival and postnatal growth. Placental structure, including organization of junctional and labyrinth zones and development of the interstitial, invasive, trophoblast lineage, were similar in mutant and wild-type mice. Akt1 and Igf2 null mutations affected postnatal growth. The relative impact of each gene differed during pre-weaning versus post-weaning growth phases. AKT1 had a more significant role during pre-weaning growth, whereas IGF2 was a bigger contributor to post-weaning growth. Akt1 and Igf2 null mutations impact placental, fetal and postnatal growth. Placental phenotypes are similar; however, fetal and postnatal growth patterns are unique to each mutation.

The pregnant motor vehicle accident casualty: adherence to basic workup and admission guidelines.

OBJECTIVE: To investigate the workup/treatment provided to pregnant motor vehicle accident (MVA) casualties in a mature trauma system. Adherence to recommendations was used to measure quality of care. BACKGROUND: MVAs affect approximately 3% of pregnant women. Trauma casualty outcome improves after implementation of guidelines. METHODS: A 5-year audit of clinical practice in 2 university hospitals with a trauma call system where the general surgeon is the primary care physician. Trauma guidelines (general/specific to treatment of pregnant MVA casualties) were used to examine adherence. Pregnant casualties aged >18 years, injured in a private vehicle were identified via computerized hospital databases. Data relevant to the study were extracted from ED/admission files. RESULTS: Among the 236 casualties included there were no maternal deaths. Six casualties (2.5%) had significant injuries and 3 (1.2%) required surgery (all within 24-hours of admission). Contrary to established procedure, maternal vital signs were often not documented. In contrast, fetal viability was usually documented; most casualties underwent ultrasound fetal evaluation (233 of 236, 98.7%) and those with viable pregnancies underwent fetal heart rate monitoring (162 of 169, 96%). A sixth of the MVA casualties (16%) were examined only by an obstetrician. All casualties were admitted but only 15 (6.4%) were admitted in accordance with guidelines. Readmission rates (1.3%) were similar to those observed in nonpregnant casualties. CONCLUSIONS: Pregnant MVA casualties are underexamined and overadmitted. Concerns regarding potential obstetrical complications distract medical attention away from basic trauma guidelines. Education programs should emphasize prioritizing the mother and adhering to the basic rules of trauma care despite the presence of the fetus.

Survival and size are differentially regulated by placental and fetal PKBalpha/AKT1 in mice.

The importance of placental circulation is exemplified by the correlation of placental size and blood flow with fetal weight and survival during normal and compromised human pregnancies in such conditions as preeclampsia and intrauterine growth restriction (IUGR). Using noninvasive magnetic resonance imaging, we evaluated the role of PKBalpha/AKT1, a major mediator of angiogenesis, on placental vascular function. PKBalpha/AKT1 deficiency reduced maternal blood volume fraction without affecting the integrity of the fetomaternal blood barrier. In addition to angiogenesis, PKBalpha/AKT1 regulates additional processes related to survival and growth. In accordance with reports in adult mice, we demonstrated a role for PKBalpha/AKT1 in regulating chondrocyte organization in fetal long bones. Using tetraploid complementation experiments with PKBalpha/AKT1-expressing placentas, we found that although placental PKBalpha/AKT1 restored fetal survival, fetal PKBalpha/AKT1 regulated fetal size, because tetraploid complementation did not prevent intrauterine growth retardation. Histological examination of rescued fetuses showed reduced liver blood vessel and renal glomeruli capillary density in PKBalpha/Akt1 null fetuses, both of which were restored by tetraploid complementation. However, bone development was still impaired in tetraploid-rescued PKBalpha/Akt1 null fetuses. Although PKBalpha/AKT1-expressing placentas restored chondrocyte cell number in the hypertrophic layer of humeri, fetal PKBalpha/AKT1 was found to be necessary for chondrocyte columnar organization. Remarkably, a dose-dependent phenotype was exhibited for PKBalpha/AKT1 when examining PKBalpha/Akt1 heterozygous fetuses as well as those complemented by tetraploid placentas. The differential role of PKBalpha/AKT1 on mouse fetal survival and growth may shed light on its roles in human IUGR.

Viable fertile mice generated from fully pluripotent iPS cells derived from adult somatic cells.

Previous studies demonstrated that induced pluripotent stem (iPS) cells could produce viable mice through tetraploid complementation, which was thought to be the most stringent test for pluripotency. However, these highly pluripotent iPS cells were previously reported to be generated from fibroblasts of embryonic origin. Achieving fully pluripotent iPS cells from multiple cell types, especially easily accessible adult tissues, will lead to a much greater clinical impact. We successfully generated high-pluripotency iPS cells from adult tail tip fibroblasts (TTF) that resulted in viable, full-term, fertile TTF-iPS animals with no obvious teratoma formation or other developmental abnormalities. Comparison of iPS cells from embryonic origin (MEF), progenitor cells (neural stem cells) or differentiated somatic cells (TTF) reveals that fully pluripotent developmental potential can be reached by each cell type, although with different induction efficiencies. This work provides the means for studying the mechanisms and regulation of direct reprogramming, and has encouraging implications for future clinical applications and therapeutic interventions.

Gestação na paciente dialítica / Pregnancy in dialysis patients

A gestação em pacientes com insuficiência renal e em terapia dialítica constitui uma situação desafiadora. Desde a sua primeira descrição em 1971, um crescente número de casos é relatado com informações conflitantes e discordantes quanto ao prognóstico materno e fetal. As principais intercorrências clínicas e obstétricas encontradas no manejo dessas pacientes são: hipertensão arterial, polidrâmnio, restrição de crescimento fetal e prematuridade. As consequências neonatais são complicações clínicas diversas, decorrentes, principalmente, da prematuridade tais como: pneumotórax, síndrome da angústia respiratória do recém-nato, sepse, enterocolite necrosante, doença pulmonar crônica, hemorragia intraventricular e surdez. Este artigo tem por objetivo revisar o tema apresentando os resultados maternos e perinatais mais recentes relatados na literatura, discutir as controvérsias no manejo dessas gestantes e apresentar a conduta obstétrica tanto no pré-natal como na assistência ao parto.

Pregnancy in insufficiency renal and dialysis patients is a challenging situation. Since its first description in 1971, a growing number of cases have been described with conflicting information about maternal and fetal outcome. The main obstetrical adverse outcomes on the management of these patients are: arterial hypertension, polihydramnios, intrauterine growth restriction and prematurity. The neonatal complications are consequences of prematurity and include pneumothorax, respiratory distress syndrome, sepsis, necrotizing entercolitis, chronic lung disease, intraventricular hemorrhage and deafness. This article aims to review the literature presenting the outcome of the most recent maternal and perinatal outcomes, discussing the controversies in the treatment of these patients and presenting the main steps in prenatal care as well as during labor.

Understanding cellular disruptions during early embryo development that perturb viability and fetal development.

An inability to regulate ionic and metabolic homeostasis is related to a reduction in the developmental capacity of the embryo. The early embryo soon after fertilisation and up until compaction appears to have a reduced capacity to regulate its homeostasis. The reduced ability to regulate homeostasis, such as intracellular pH and calcium levels, by the precompaction-stage embryo appears to impact on the ability to regulate mitochondrial function and maintain adequate levels of energy production. This reduction in ATP production causes a cascade of events leading to disrupted cellular function and, perhaps ultimately, disrupted epigenetic regulation and aberrant placental and fetal development. In contrast, after compaction the embryo takes on a more somatic cell-like physiology and is better able to regulate its physiology and therefore appears less vulnerable to stress. Therefore, for human IVF it would seem important for the establishment of healthy pregnancies that the embryos are maintained in systems that are designed to minimise homeostatic stress, particularly for the cleavage-stage embryos, as exposure to stress is likely to culminate in impaired embryo function.

Anaesthesia for non-obstetric surgery during pregnancy.

As with all anaesthesia, the fundamentals of physiology, pharmacology and pathology must be understood, as well as an appreciation of the effects of drugs on the mother and fetus when providing anaesthesia care in pregnancy. Hypothermic, hyperbaric, cardiac by-pass, hypotensive and other special techniques have been used safely in pregnancy. If these are contemplated then the anaesthetist should consult expert help. [A disk copy of the slides and all references cited in the lecture are available on request from the author].

Expression of the insulin-like growth factor-1 gene and its receptor in preimplantation mouse embryos; is it a marker of embryo viability?

Recent studies have demonstrated the importance of insulin-like growth factors (IGF) in mouse preimplantation development. We examined IGF-1 and IGF-1 receptor (IGF-1R) gene expression in a single blastomere of an early mouse embryo and compared it with subsequent embryo development in culture. Fertilized eggs and 2-cell embryos were obtained by tubal flushing in superovulated and mated female mice. Single cells were removed from embryos at cleavage stage between 3 and 8 cells using the standard embryo biopsy techniques. Individual blastomeres from each embryo were then assayed for the presence of IGF-1 and IGF-1R mRNA using reverse transcription-polymerase chain reaction. The biopsied embryos were washed in medium and placed in co-culture with murine endometrial cells. Embryonic development in culture was assessed and blastocyst grading was performed. IGF-1 gene expression was then examined for an association with in-vitro development. Eighty-seven embryos were biopsied. IGF-1R gene expression was detected in the majority of embryos tested and IGF-1 gene expression was detected in 34 of 81 (42%) embryos. A significant association between IGF-1 expression and blastocyst formation in vitro was found (P < 0.01). There was no association between IGF-1R expression and subsequent embryo development. We conclude that IGF-1 gene expression could potentially be used as a marker of embryo quality.