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Journal of Experimental & Clinical Assisted Reproduction is an open access, online, peer-review journal publishing papers on all aspects of research into reproductive endocrinology, infertility, bioethics and the advanced reproductive technologies. The journal reports on important developments impacting the field of human reproductive medicine and surgery. The field exists as a sub-specialty of obstetrics & gynecology, focusing on the diagnosis and treatment of complex human reproductive problems. The continued growth of this relatively new field depends on quality research by proven scientists as well as junior investigators who, together, make contributions to this area of medical and surgical practice. The publishing revolution made possible by internet technology presages a bright future for continued interdisciplinary collaboration among researchers. Against this background, Journal of Experimental & Clinical Assisted Reproduction exists for the scientific community to facilitate this scholarly dialogue.

SUMMARY

This article looks at medical approaches to women’s fertility in Argentina in the 1930s and explores the ways in which eugenics encouraged the reproduction of the fit and attempted to avoid the reproduction of the unfit. The analysis concentrates on three main aspects: biotypology (the scientific classification of bodies), endocrine therapy, and sterilization. The article concludes by suggesting that a eugenically oriented obstetrical and gynecological practice encouraged both endocrine treatments (to achieve the ideal fertile woman) and sterilization, which, in spite of being legally banned, found a subtle application.

Birds are some of the most familiar organisms of global ecosystems. Changes in the visibility and abundance of birds are therefore excellent indicators of population and physiological responses to habitat changes and are a major focus for public concern about detrimental environmental changes. In order to understand how birds respond to these challenges, it is essential to determine how the environment affects reproduction under natural conditions. The continuum from environmental variables (cues) to reproductive life-history traits depends upon a cascade of neural and physiological processes that determine the extent and rate at which birds will be able to adapt to changes in their environment. For a full understanding of this ability to adapt, ecologists and endocrinologists need to collaborate and build a common framework. The objective of this theme issue is to bring together a series of papers addressing how evolutionary ecologists and endocrinologists can collaborate directly using avian reproduction as a model system. First, we address the need to integrate ecology and endocrinology and what benefits to biological knowledge will be gained. The papers collected in this issue represent a new synthesis of ecology and endocrinology as discussed in three E-BIRD workshops. The three main foci are trade-offs and constraints, maternal effects and individual variation. Authors within each group present ecological and endocrinological aspects of their topics and many go on to outline testable hypotheses. Finally, we discuss where the major problems remain and how this issue points out where these need collaborative efforts of ecologists and endocrinologists. Specific challenges are raised to future researchers to break through intellectual barriers and explore new frontiers. This framework of topics will ultimately apply to all taxa because the principles involved are universal and hopefully will have direct application to programmes integrating organisms and genes throughout biological sciences.

During the past decade, the immune and endocrine systems have been discovered to interact in controlling physiologic processes as diverse as cell growth and differentiation, metabolism, and even human and animal behavior. The interaction between these two major physiological systems is a bi-directional process. While it has been well documented that hormones, including prolactin (PRL), growth hormone (GH), insulin-like growth factor-I (IGF-I), and thyroid-stimulating hormone (TSH), regulate a variety of immune events, a great deal of data have accumulated supporting the notion that cytokines from the innate immune system also affect the neuroendocrine system. Communication between these two systems coordinates processes that are necessary to maintain homeostasis. Proinflammatory cytokines often act as negative regulatory signals that temper the action of hormones and growth factors. This system of ‘checks and balances’ is an active, ongoing process, even in healthy individuals. Dysregulation of this process has been implicated as a potential pathogenic factor in the development of co-morbid conditions associated with several chronic inflammatory diseases, including type 2 diabetes, cardiovascular disease, cerebrovascular disease, inflammatory bowel disease, rheumatoid arthritis, major depression and even normal aging. Over the past decade, research in our laboratory has focused on the ability of the major proinflammatory cytokines, tumor necrosis factor (TNF)α and interleukin (IL)-1β, to induce a state of IGF resistance. This review will highlight these and other new findings by explaining how proinflammatory cytokines induce resistance to the major growth factor, insulin-like growth factor-I (IGF-I). We also highlight that IGF-I can induce resistance or reduce sensitivity to brain TNFα and discuss how TNFα, IL-1β and IGF-I interact to regulate several aspects of behavior and cognition.

Objective:

To provide background information on methodologic factors that influence and add variance to endocrine outcome measurements. Our intent is to aid and improve the quality of exercise science and sports medicine research endeavors of investigators inexperienced in endocrinology.

Background:

Numerous methodologic factors influence human endocrine (hormonal) measurements and, consequently, can dramatically compromise the accuracy and validity of exercise and sports medicine research. These factors can be categorized into those that are biologic and those that are procedural-analytic in nature.

Recommendations:

Researchers should design their studies to monitor, control, and adjust for the biologic and procedural-analytic factors discussed within this paper. By doing so, they will find less variance in their hormonal outcomes and thereby will increase the validity of their physiologic data. These actions can assist the researcher in the interpretation and understanding of endocrine data and, in turn, make their research more scientifically sound.

Macaques provide excellent models for preclinical testing and safety assessment of female reproductive toxicants. Currently, cynomolgus monkeys are the predominant species for (reproductive) toxicity testing. Marmosets and rhesus monkeys are being used occasionally. The authors provide a brief review on physiology and endocrinology of the cynomolgus monkey ovarian cycle, practical guidance on assessment and monitoring of ovarian cyclicity, and new data on effects of social housing on ovarian cyclicity in toxicological studies. In macaques, cycle monitoring is achieved using daily vaginal smears for menstruation combined with cycle-timed frequent sampling for steroid and peptide hormone analysis. Owing to requirements of frequent and timed blood sampling, it is not recommended to incorporate these special evaluations into a general toxicity study design. Marmosets lack external signs of ovarian cyclicity, and cycle monitoring is done by regular determinations of progesterone. Cynomolgus and marmoset monkeys do not exhibit seasonal variations in ovarian activity, whereas such annual rhythm is pronounced in rhesus monkeys. Studies on pair- and group-housed cynomolgus monkeys revealed transient alterations in the duration and endocrinology of the ovarian cycle followed by return to normal cyclicity after approximately six months. This effect is avoided if the animals had contact with each other prior to mingling. These experiments also demonstrated that synchronization of ovarian cycles did not occur.

In conditions characterized by energetic constraints, such as in periods of low food availability, some trade-offs between reproduction and self-maintenance may be necessary; even year-round breeders may then be forced to exhibit some reproductive seasonality. Prior research has largely focused on female reproduction and physiology, and few studies have evaluated the impact of environmental factors on males. Here we assessed the effects of season and ambient temperatures on fecal glucocorticoid (fGC) and testosterone (fT) levels in male baboons in Amboseli, Kenya. The Amboseli basin is a highly challenging, semi-arid tropical habitat that is characterized by strongly seasonal patterns of rainfall and by high ambient temperatures. We previously reported that female baboons were impacted by these challenging environmental conditions. We ask here whether male baboons in the same environment and groups as females exhibit similar physiological effects. We found that after accounting for male age and individual variability, males exhibited higher fGC levels and lower fT levels during the dry season than during the wet season. Furthermore, fT but not fGC levels were lower in months of high average daily maximum temperatures, suggesting a direct impact of heat on testes. Our results demonstrate that male baboons, like females, experience ecological stress that alters their reproductive physiology. The impact of the environment on male reproduction deserves more attention both in its own right and because alteration in male physiology may contribute to the reduction in female fertility observed in challenging environments.

The endocrinology of the aging male is complex, with multiple hormones along the hypothalamic-pituitary-testicular (HPT) axis interacting with one another in feedback. As men age, there is a small and progressive (not precipitous, as in women) decline in several sex hormones, in particular testosterone and dehydroepiandrosterone, and related increases in luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin. The importance of these changes is wide-ranging because of the ubiquitous role of sex hormones in male physiology. This chapter discusses the endocrinology of the aging male. We provide an overview of the regulation of the HPT axis with an emphasis on the changes that occur with aging and the measurement of gonadal steroids, including hormone pulsatility, within-subject and circadian variations. The difficulties of assessing the symptoms of late-onset hypogonadism are highlighted. There is a comprehensive discussion of the epidemiology of sex hormone changes, including their age associations, prevalence of symptomatic hypogonadism, secular changes, risk factors, and the association of sex hormones with outcomes.

Most steroid disorders of the adrenal cortex come to clinical attention in childhood and in order to investigate these problems, there are many challenges to the laboratory which need to be appreciated to a certain extent by clinicians. The analysis of sex steroids in biological fluids from neonates, over adrenarche and puberty present challenges of specificities and concentrations often in small sample sizes. Different reference ranges are also needed for interpretations. For around 40 years, quantitative assays for the steroids and their regulatory peptide hormones have been possible using immunoassay techniques. Problems are recognised and this review aims to summarise the benefits and failings of immunoassays and introduce where tandem mass spectrometry is anticipated to meet the clinical needs for steroid analysis in paediatric endocrine investigations. It is important to keep a dialogue between clinicians and the laboratory, especially when any laboratory result does not make sense in the clinical investigation.

Conflict of interest:None declared.

Trophoblast differentiation and formation of the placenta are important events linked to post-implantation embryonic development. Models mimicking the biology of trophoblast differentiation in a post-implantation maternal microenvironment are needed for understanding disorders like placental-ischemia or for applications in drug-screening, and would help in overcoming the ethical impasse on using human embryos for such research. Here we attempt to create such a model by using embryoid bodies (EBs) and a biomimetic platform composed of a bilayer of fibronectin and gelatin on top of low-melting agarose. Using this model we test the hypothesis that cystic-EBs (day 30) that resemble blastocysts morphologically, are better sources as compared to noncytic EBs (day 10), for functional trophoblast differentiation; and that the Rho kinases inhibitor Y27632 can enhance this differentiation. Non/cytic EBs with/out Y27632 were grown on this platform for 28 days, and screened from secretion and expression of trophoblast and other lineage markers using ECLIA, RT-PCR, and Immunofluorescence. All EBs attached on this surface and rapidly proliferated into hCG and progesterone (P2) secreting functional trophoblast cells. However, the cells derived from cytic-EBs and cytic-EBs+ Y27632 showed the maximum secretion of these hormones and expressed IGF2, supporting our hypothesis. Also Y27632 reduced extraembryonic endoderm and trophoblast lineage differentiation from early noncystic-EBs, whereas, it specifically enhanced the induction of trophoblast and multinucleated syncitiotrophoblast differentiation from late cystic-EBs. In vivo trophoblast differentiation can be replicated in fibronectin based biomaterials, using cytic-EBs and by maneuvering the Rho-ROCK pathways. Response of EBs to a compound may vary temporally, and determination of their right stage is crucial for applications in directed-differentiation or drug-screening.

Background

This research describes current clinical and demographic features sampled from reproductive endocrinology programs currently offering in vitro fertilization (IVF) in the Middle East.

Methods

Clinic leadership provided data via questionnaire on patient demographics, demand for IVF services, annual cycle volume, indications for IVF, number of embryos transferred, twinning frequency, local regulations governing range of available adjunct therapies, time interval between initial enrollment and beginning IVF as well as information about other aspects of IVF at each center.

Results

Data were received from representative IVF clinics (n = 13) in Cyprus, Egypt, Iran, Israel, Jordan, Lebanon, Qatar, Saudi Arabia and Turkey. Mean (± SD) age of respondents was 47.8 ± 8 yrs, with average tenure at their facility of 11.2 ± 6 yrs. Estimated total number of IVF programs in each nation responding ranged from 1 to 91. All respondents reported individual participation in accredited CME activity within 24 months. 76.9% performed embryo transfers personally; blastocyst transfer was available at 84.6% of centers. PGD was offered at all sites. In this population, male factor infertility accounted for most IVF consultations and the majority (59.1%) of female IVF patients were < 35 yrs of age. Prevalence of smoking among female IVF patients was 7.2%. Average number of embryos transferred was 2.4 (± 0.4) for patients at age < 35 yrs, and 2.9 (± 0.8) at age > 41 yrs. For these age categories, twinning (any type) was observed in 22.6 (± 10.8)% and 13.7 (± 10.4)%, respectively. In 2005, the average number of IVF cycles completed at study sites was 1194 (range 363–3500) and 1266 (range 263–4000) in 2006. Frozen embryo transfers accounted for 17.2% of cycles at these centers in 2005. Average interval between initial enrollment and IVF cycle start was 8 weeks (range 0.3–3.5 months).

Conclusion

This sampling of diverse IVF clinics in the Middle East, believed to be the first of its kind, identified several common factors. Government registry or oversight of clinical IVF practice was limited or nonexistent in most countries, yet number of embryos transferred was nevertheless fairly uniform. Sophisticated reproductive health services in this region are associated with minimal delay (often < 8 weeks) from initial presentation to IVF cycle start. Most Middle East nations do not maintain a comprehensive IVF database, and there is no independent agency to collect transnational data on IVF clinics. Our pilot study demonstrates that IVF programs in the Middle East could contribute voluntarily to collaborative network efforts to share clinical data, improve quality of care, and increase patient access to reproductive services in the region.

This report concerns two new cases of the Cohen syndrome and gives further information on the variable phenotypical pattern of the disease. The frequency of major and minor clinical signs is reviewed from all the published reports. Among the minor signs we found previously undescribed skeletal abnormalities in one of our patients. The reported delay onset of puberty, which appears to be a frequent aspect of the syndrome, seems to occur without LH and FSH deficiency, as our patients show.

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The following project aimed at promoting integrated and long-lasting learning is described for an Immunology course, but it may be adapted to other disciplines. Students were asked to develop and carry out a research project to examine the relationship between immune function and stress. The experiments were required to include the assessment of salivary cortisol and salivary IgA (sIgA) with enzyme immunoassays. All other aspects of the experiments were developed by student groups with appropriate guidance from the instructor. Data are presented for one group project that assessed the effect of music on cortisol and sIgA. Overall levels of sIgA and cortisol were consistent with reported values. Students found a significant decrease in cortisol over time. Additionally, there was a trend that supported the overall student hypothesis regarding the effect of stress and immune function. Compared with the same Immunology course that included an instructor-designed experiment using enzyme immunoassays for cortisol and sIgA, several assessments (e.g., final grades and comments on student evaluations) show that overall learning seemed to be much better in the course with the student-directed research project.

OBJECTIVE--To determine the views of a large and representative group of consultant physicians on the Calman proposals, in which acute general medical services will change from being primarily consultant led to consultant provided. DESIGN--Postal questionnaires. SUBJECTS--All 236 consultant physicians in acute hospitals in North West and South West Thames regions. RESULTS--Replies were received from 179 (76%). One hundred and thirty seven (77%) indicated that they would not resume emergency residential duties, and 126 (71%) indicated that they would probably withdraw from general medical duties under these circumstances. One hundred and twenty six (70%) and 137 (77%) had not inserted a central venous line or temporary pacemaker, respectively, within the previous five years. Of 157 answering a question on the impact of the Calman proposals on the quality of patient services, 125 considered that it would be detrimental, and only 18 (11%) thought that it would be beneficial. CONCLUSION--Most consultant physicians are not prepared to resume emergency duties and could not do so without retraining in practical procedures. There is widespread antagonism to the Calman proposals, and most physicians consider that their impact on the quality of patient services will be detrimental.

Brazil is a large, populous country in South America, which has one of the biggest concentrations of people with diabetes. This article reviews the current status of diabetes care, medical education and training, and diabetes/endocrine research in Brazil. It highlights achievements in public health and research, which can be emulated by other countries. In Endocrine/Diabetes fields, a more realistic and responsible policies in terms of medical traineeship, patient education, and mainly scientific production would be mandatory to raise Brazil to a global competitive level.

Thailand is a developing country in Southeast Asia with a nationally acknowledged requirement for improvement of the medical system. At present, endocrinology is a specific branch of medicine that is taught in few medical schools. There are very few endocrinologists in Thailand, who are unable to cope with the large number of patients with endocrinology problems. Primary care for common endocrine disorders, such as diabetes mellitus and thyroid disease, is still the domain of general practitioners. In this article, the author will present unique challenges and unique solutions of endocrinology practice in Thailand.

Until recently, congenital adrenocortical hyperplasia has defied most medical and surgical therapeutic efforts. However, in properly selected patients, cortisone will suppress the abnormal cortical hormone production. This, in turn, will lead to previously inhibited maturation and developmental progress.

Adrenocortical insufficiency calls for much diagnostic alertness, as early recognition and immediate treatment are of paramount importance. The available therapeutic means are beneficial, although their limitations and potential dangers should be heeded.

Among newly developed diagnostic techniques, thyrograms promise to be helpful in the study of thyroid hyperplasia and neoplasia. Thyroid cancer, occurring infrequently in childhood, should at the earliest possible time be treated surgically and with postoperative radiation therapy.

Background

This study assessed pharmacy performance and satisfaction as reported by patients during ovulation induction therapy.

Materials and methods

Patients (n = 1269) receiving gonadotropin prescriptions for intrauterine insemination or in vitro fertilisation-embryo transfer in 2007–2008 were prospectively interviewed by nurses and/or completed a structured questionnaire to evaluate pharmacy performance. "Community" (n = 12) and "specialty" (n = 2) pharmacy status (C vs. S) was defined by each pharmacy, and all pharmacies were selected by patients before cycle start. Patient comments about their pharmacy were classified into five types: i) Dispensing error-gonadotropin, ii) Dispensing error-non gonadotropin, iii) Mistake in prescribed medical equipment/supplies, iv) Counselling/communication inaccuracy, and v) Inventory problem or other.

Results

391 pharmacy concerns were reported from 150 fertility patients during the study period. The majority (75.9%) of patients selected a S pharmacy to fill their prescriptions, and this pharmacy type was identified in 2.8% of adverse pharmacy encounters (p < 0.0001). Non-gonadotropin prescriptions filled at C pharmacies accounted for 40.2% of all complaints, followed by problems with prescriptions for supplies (20.2%) and gonadotropins (18.7%) at C pharmacies. Patient conflict involving S pharmacies was limited (n = 11), and related to operating hours and medication delivery logistics.

Conclusion

Fertility patients reported a disproportionate and significantly higher number of adverse pharmacy encounters from C pharmacies compared to S pharmacies. Although no licensing mechanism in Ireland currently recognises special training or certification in any area of pharmacy practice, informal self-designations by pharmacies remain a useful discriminator. Level of familiarity with fertility medicines and availability of inventory are important characteristics to be considered when counselling fertility patients about pharmacy choice. Those who select a C pharmacy should be advised to allow extra time for inventory verification, order confirmation, and additional counselling. Additional study is needed to determine if a minimum volume of fertility-related prescriptions is necessary to assure competence in this particular field of pharmacy practice.

Hirsutism represents a primary clinical indicator of androgen excess. The most common endocrine condition causing hirsutism is polycystic ovary syndrome (PCOS). Diagnosing PCOS is not easy as the signs and symptoms are heterogenous. The newest diagnostic guideline made by the Androgen Excess and PCOS Society in 2006, claims the presence of hyperandrogenism, and ovarian dysfunction (oligo / anovulation and / or polycystic ovaries). Obesity associated reproductive and metabolic dysfunctions may aggravate the symptoms of PCOS. PCOS might be underdiagnosed in non obese women because lean PCOS phenotypes might be underestimated for the syndrome. Effective medical treatment of PCOS and associated hirsutism depends on the endocrinological expertise and experience of the therapist in each individual case. An algorithm for the treatment has not been established yet.

Preeclampsia is a leading cause of maternal and fetal/neonatal mortality and morbidity worldwide. The early identification of patients with an increased risk for preeclampsia is therefore one of the most important goals in obstetrics. The availability of highly sensitive and specific physiologic and biochemical markers would allow not only the detection of patients at risk but also permit a close surveillance, an exact diagnosis, timely intervention (e.g. lung maturation), as well as simplified recruitment for future studies looking at therapeutic medications and additional prospective markers. Today, several markers may offer the potential to be used, most likely in a combinatory analysis, as predictors or diagnostic tools. We present here the current knowledge on the biology of preeclampsia and review several biochemical markers which may be used to monitor preeclampsia in a future, that, we hope, is not to distant from today.

Background

Professional working at computer notebooks is associated with high requirements on the body posture in the seated position. By the high continuous static muscle stress resulting from this position at notebooks, professionals frequently working at notebooks for long hours are exposed to an increased risk of musculoskeletal complaints. Especially in subjects with back pain, new notebooks should be evaluated with a focus on rehabilitative issues.

Methods

In a field study a new notebook design with adjustable screen was analyzed and compared to standard notebook position.

Results

There are highly significant differences in the visual axis of individuals who are seated in the novel notebook position in comparison to the standard position. Also, differences are present between further alternative notebook positions. Testing of gender and glasses did not reveal influences.

Conclusion

This study demonstrates that notebooks with adjustable screen may be used to improve the posture. Future studies may focus on patients with musculoskeletal diseases.

The discovery of fetal mRNA transcripts in the maternal circulation holds great promise for noninvasive prenatal diagnosis. To identify potential fetal biomarkers, we studied whole blood and plasma gene transcripts that were common to 9 term pregnant women and their newborns but absent or reduced in the mothers postpartum. RNA was isolated from peripheral or umbilical blood and hybridized to gene expression arrays. Gene expression, paired Student’s t test, and pathway analyses were performed. In whole blood, 157 gene transcripts met statistical significance. These fetal biomarkers included 27 developmental genes, 5 sensory perception genes, and 22 genes involved in neonatal physiology. Transcripts were predominantly expressed or restricted to the fetus, the embryo, or the neonate. Real-time RT-PCR amplification confirmed the presence of specific gene transcripts; SNP analysis demonstrated the presence of 3 fetal transcripts in maternal antepartum blood. Comparison of whole blood and plasma samples from the same pregnant woman suggested that placental genes are more easily detected in plasma. We conclude that fetal and placental mRNA circulates in the blood of pregnant women. Transcriptional analysis of maternal whole blood identifies a unique set of biologically diverse fetal genes and has a multitude of clinical applications.

Introduction

Maternal body mass index has an impact on maternal and fetal pregnancy outcome. An increased maternal BMI is known to be associated with admission of the newborn to a neonatal care unit. The reasons and impact of this admission on fetal outcome, however, are unknown so far.

Objective

The aim of our study was to investigate the impact of maternal BMI on maternal and fetal pregnancy outcome with special focus on the children admitted to a neonatal care unit.

Methods

A cohort of 2049 non-diabetic mothers giving birth in the Charite university hospital was prospectively studied. The impact of maternal BMI on maternal and fetal outcome parameters was tested using multivariate regression analysis. Outcome of children admitted to a neonatal ward (n = 505) was analysed.

Results

Increased maternal BMI was associated with an increased risk for hypertensive complications, peripheral edema, caesarean section, fetal macrosomia and admission of the newborn to a neonatal care unit, whereas decreased BMI was associated with preterm birth and lower birthweight. In the neonatal ward children from obese mothers are characterized by hypoglycaemia. They need less oxygen, and exhibit a shorter stay on the neonatal ward compared to children from normal weight mothers, whereas children from underweight mothers are characterized by lower umbilical blood pH and increased incidence of death corresponding to increased prevalence of preterm birth.

Conclusion

Pregnancy outcome is worst in babies from mothers with low body mass index as compared to healthy weight mothers with respect to increased incidence of preterm birth, lower birth weight and increased neonate mortality on the neonatal ward. We demonstrate that the increased risk for neonatal admission in children from obese mothers does not necessarily indicate severe fetal impairment.

Adverse events in utero can be critical in determining quality of life and overall health. It is estimated that up to 50 % of metabolic syndrome diseases can be linked to an adverse fetal environment. However, the mechanisms linking impaired fetal development to these adult diseases remain elusive. This review uncovers some of the molecular mechanisms underlying how normal physiology may be impaired in fetal and postnatal life due to maternal insults in pregnancy. By understanding the mechanisms, which include epigenetic, transcriptional, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS), we also highlight how intervention in fetal and neonatal life may be able to prevent these diseases long-term.

Fetal surgery has come of age. For decades experimental fetal surgery proved essential in studying normal fetal physiology and development, and pathophysiology of congenital defects. Clinical fetal surgery started in the 1960s with intrauterine transfusions. In the 1970s, the advent of ultrasonography revolutionized fetal diagnosis and created a therapeutic vacuum. Fetal treatment, medical and surgical, is slowly trying to fill the gap. Most defects detected are best treated after birth, some requiring a modification in the time, mode and place of delivery for optimal obstetrical and neonatal care. Surgical intervention in utero should be considered for malformations that cause progressive damage to the fetus, leading to death or severe morbidity; that can be corrected or palliated in utero with a reasonable expectation of normal postnatal development; that cannot wait to be corrected after birth, even considering pre-term delivery; that are not accompanied by chromosomal or other major anomalies. At present, congenital hydronephrosis is the most common indication for fetal surgery, followed by obstructive hydrocephalus. Congenital diaphragmatic hernia also fulfills the criteria, but its correction poses more problems, and no clinical attempts have been reported so far. In the future many other malformations or diseases may become best treated in utero. The ethical and moral issues are complex and need to be discussed as clinical and experimental progress is made.