Cigarette smoke is associated with up-regulation of inducible NOS and COX-2 protein expression and activity in granulosa cells of women undergoing in vitro fertilization.

Cigarette smoke exposure represents a well-established ovotoxic exogenous stress, but the molecular mechanisms underlying of this effect are still unclear. Cigarette smoke upregulates inflammatory genes in the female reproductive organs, therefore an abnormal inflammation response may contribute to the impairment of female fertility. In this study we investigated for the first time the effect of cigarette smoke exposure on NOS and COX expression and activity and on their transcription factors (CREB and NF-kB) in human GCs and on the release of NO and PGE2 in the FF in smoking and non-smoking patients undergoing IVF treatment. In addition, correlation analysis between AMH serum levels, an index of ovarian reserve, and smoking exposure or iNOS and COX-2 protein expression levels were performed using a Pearson correlation method. Cigarette smoke exposure resulted in a significant increase of iNOS and COX-2 protein expression together with an increase of iNOS activity and PGE2 levels. pNF-kB and pCREB protein expression were upregulated in the GCs of smokers compared to non-smokers. The habit of smoking was negatively correlated with serum AMH levels, and positively correlated with iNOS and COX-2 protein expression levels. The data presented in the current study revealed a novel molecular mechanism underlying the toxic effects of cigarette smoke on fertility. Additional pathways mediating the effects of cigarette smoke exposure in human GCs cannot be excluded and should be investigated in future studies.

Non-O blood group and outcomes of in vitro fertilization.

PURPOSE: Retrospective and cross-sectional studies suggested that non-O blood group may be associated with failures of in vitro fertilization (IVF), but data remain controversial. The aim of this observational cohort study was to prospectively evaluate the effect of non-O blood type on clinical outcomes of IVF. METHODS: Women < 40 years who underwent IVF and had ABO blood type recorded as part of the routine workup were eligible. The primary study outcome was live birth. Secondary outcomes included spontaneous abortion, positive pregnancy test, and clinical pregnancy. RESULTS: A total of 497 women with a mean age of 34.6 (standard deviation 3.2) years were included. The mean number of embryos transferred was 2.3 (standard deviation 0.6). The most common ABO blood types were O (n = 213, 42.9%) and A (n = 203, 40.8%), while 63 (12.7%) and 18 (3.6%) women had the B and AB blood types, respectively. Differences in live birth (21.8 vs. 24.3%, odds ratio [OR] 1.17; 95% confidence intervals [CI], 0.76 to 1.78), positive pregnancy test (37.9 vs. 36.6%, OR 0.96; 95% CI, 0.66 to 1.38), clinical pregnancy (35.1 vs. 33.8%, OR 0.95; 95% CI, 0.66 to 1.39), and spontaneous abortion (12.3 vs. 9.2%, OR 0.72; 95% CI, 0.41 to 1.29) between women with O and non-O blood type were not statistically significant. CONCLUSIONS: In a prospective cohort study, we confirmed the lack of a significant association between non-O blood type and clinical outcomes of IVF. Further studies are needed to clarify whether non-O blood group has any prognostic relevance in women undergoing IVF.

Mole modifications following controlled ovarian stimulation for assisted reproduction technologies.

BACKGROUND: The role of estrogens on moles biology remains undefined although estrogenic receptors have been found on melanocytes. It has been postulated that supraphysiological estrogen levels could promote the progression of moles to melanoma. Women undergoing controlled ovarian stimulation (COS) for assisted reproductive technologies (ART) are exposed to high levels of estrogens, produced by the ovary in response to exogenous gonadotropin administration. The aim of this study is to assess whether COS for ART may have an impact on mole structure and/or characteristics. METHODS: Women undergoing to ART for various infertility conditions were included in the study. Personal and clinical data were collected. Dermatoscopic features and scores (total dermoscopy score--TDS) were statistically compared before COS and after a 6-month follow-up period. Statistical correlation was performed between estradiol, FSH blood levels and relative variation in moles dimensions. RESULTS: A total of 46 patients were included in the study. One hundred and seventy-five melanocytic lesions from 31 patients were evaluated at both time points. Although statistically significant differences were found in mole dimension and TDS between the two time points, these differences had no relevance in the clinical setting not suggesting the need for mole excision. Moreover, the only statistically significant correlation with estradiol blood concentration on hCG administration day was found with one-axis dimensional variation. CONCLUSIONS: To our knowledge this is the first work to evaluate the effect of COS on moles. The obtained results do not support a causal relation between the supraphysiological hormone levels stimulation and worsening of clinical and dermoscopical features of moles. Further study is needed to clarify whether estrogens plays a role in melanoma.

Developmental neurotoxicity and anticonvulsant drugs: a possible link.

In utero exposure to antiepileptic drugs (AEDs) may affect neurodevelopment causing postnatal cognitive and behavioral alterations. Phenytoin and phenobarbital may lead to motor and learning dysfunctions in the pre-exposed children. These disorders may reflect the interference of these AEDs with the development of hippocampal and cerebellar neurons, as suggested by animal studies. Exposure to valproic acid may result in inhibition of neural stem cell proliferation and/or immature neuron migration in the cerebral cortex with consequent increased risk of neurodevelopmental impairment, such as autistic spectrum disorders. A central issue in the prevention of AED-mediated developmental effects is the identification of drugs that should be avoided in women of child-bearing potential and during pregnancy. The aim of this review is to explore the possible link between AEDs and neurodevelopmental dysfunctions both in human and in animal studies. The possible mechanisms underlying this association are also discussed.

Morphometric and ultrastructural analysis of human granulosa cells after gonadotrophin-releasing hormone agonist or antagonist.

Morphological features of granulosa cells can reflect their functional status. The present study was aimed at comparing possible differences in the fine structure of human granulosa cells exposed to gonadotrophin-releasing hormone (GnRH) agonist or antagonist treatment during ovarian stimulation. Cells were obtained from follicular aspirates of 21 women treated with recombinant follicle-stimulating hormone (rFSH) plus either a GnRH agonist or a GnRH antagonist. Conventional light microscopy procedures and computerized image analysis systems were used to identify different cell type morphological patterns and to quantify different cells distribution. Two morphologically distinct granulosa cell populations, defined as large/pale and small/dark cells, were identified and a different distribution in the two groups of women under investigation was found: a significantly higher percentage in large/pale cells was detected in the agonist-treated women (P<0.05), whereas the percentage of small/dark cells was significantly higher in the antagonist-treated group (P<0.05). Ultrastructural observations showed the presence in both cell populations of typical hallmarks of steroidogenic cells, highlighting signs of functional activity in the large/pale cell population. Further investigations are needed to define the possible clinical significance of these morphological findings.

Impact of estrogen replacement on letrozole-induced embryopathic effects.

BACKGROUND: The aromatase inhibitor, letrozole, exerts embryo toxic effects in rats, causing increased embryo lethality and anomalies of the axial skeleton at pharmacologically relevant doses. Letrozole acts by inhibiting estrogen biosynthesis. It may thus be feasible that estrogen deprivation is a crucial determinant of the elicited developmental toxic effects. In order to gain insight on this hypothesis, the present study tested the capacity of estrogen replacement in preventing letrozole-mediated embryopathy. METHODS: Pregnant Sprague Dawley rats were exposed to letrozole alone (0.04 mg/kg), or in combination with estradiol cyclopentylpropionate (ECP) at 0.5, 1 or 2 microg/rat. A control group receiving only the vehicles was also included. Animals were exposed during gestation Days 6-16 (corresponding approximately to 3-10 weeks of gestation in the human). Developmental end-points, including intrauterine mortality, fetal growth, placental weight and incidence of structural abnormalities, were evaluated near term gestation. RESULTS: Exposure to letrozole alone was lethal for 41% of conceptuses, and caused minor axial skeletal anomalies in 51% of live fetuses. ECP co-administration effectively prevented letrozole-induced embryolethality, but failed to reduce the incidence of axial skeletal alterations. CONCLUSION: The obtained results support the concept that inhibition of estrogen biosynthesis represents a critical determinant of letrozole-induced embryonic mortality. A mechanism other than estrogen deprivation appears to underlie the initiation of skeletal anomalies.

Pampiniform plexus and oxidative stress during chronic hypoxia and hyperoxia.

The aim of the present study is to investigate oxidative stress produced by experimental hypoxia and hyperoxia in young and old pampiniform plexus rats, in order to evaluate the oxidative role of oxygen. Oxidative stress causing molecular and cellular dysfunction increases in hypertension and can therefore be considered a state of oxidative stress. This consideration makes us reflect on the responsibility of oxidative stress in the veins of the pampiniform plexus, notoriously under high hydrostatic pressure. After experimental hypoxia and hyperoxia we studied the 8-iso-PGF2alpha release (a specific index of cellular oxidative stress) in young and old left pampiniform plexus rats. The basal 8-iso-PGF2alpha release showed a statistically significant difference P=0.0067 between young and old rats PP. After hypoxia and hyperoxia, the release was higher in young rats as compared to normoxia, respectively P=0.0001 and P=0.0002. After hypoxia the release was not modified in old rats P=0.544 while after hyperoxia the release was increased in old rats as compared to control P less than 0.0001. The results show how chronic hypoxia and hyperoxia represent two important causes of oxidative stress and lipid peroxidation in pampiniform plexus rats. In young rats an increase of oxidative stress suggests that pampiniform plexus is sensitive to variations of oxygen supply. In old rats the pampiniform plexus is liable to a reduction of oxygen-sensing mechanisms and it is possible that the missing oxidative answer to the hypoxia in old rats is attributable in all likelihood to adaptation to a hypoxic condition typical of aging.

Effects of the aromatase inhibitor letrozole on in utero development in rats.

BACKGROUND: The aromatase inhibitor letrozole has recently been identified as a promising ovulation-inducing agent. As information regarding possible adverse effects on gestation outcome is limited, the present study was undertaken to evaluate the developmental toxicity potential of letrozole in the rat. METHODS: Pregnant Sprague-Dawley rats were exposed via drinking water to letrozole at 0 (control group), 0.01, 0.02, or 0.04 mg/kg during the period of organogenesis. Developmental endpoints, including intrauterine mortality, fetal growth and incidence of structural abnormalities, were evaluated near the end of gestation. RESULTS: Major treatment-related effects included: (i) a dose-dependent increase in post-implantation loss, which reached 47.2% following exposure to 0.04 mg/kg letrozole; (ii) minor vertebral anomalies affecting 32.2, 29.3 and 42.2% of fetuses exposed to 0.01, 0.02 and 0.04 mg/kg, respectively. CONCLUSION: Gestational exposure to doses of letrozole that are equal to or lower than the daily recommended human dose has toxic effects on prenatal development in rats.

Prevalence of chromosomal abnormalities in 2078 infertile couples referred for assisted reproductive techniques.

BACKGROUND: This study analyses the prevalence of karyotype changes and Yq11 microdeletions among couples referred for assisted reproduction techniques. METHODS: Prior to receiving either IVF or ICSI treatment, each partner of 2078 infertile couples was screened for karyotype changes by GTG-banding technique on peripheral lymphocytes. No subject presented with obvious phenotype of chromosomal rearrangement. All the oligo/azoospermic men with normal karyotype were further investigated by PCR for Yq11 microdeletions. RESULTS: Eighty-two out of 2078 couples (3.95%) had one partner carrying a chromosomal change, and 10 out of 202 (4.95%) men showed Yq11 microdeletions. The chromosomal rearrangements were 44 (2.1%) translocations, 23 (1.1%) gonosomal mosaics, six (0.3%) 47,XXY, five (0.24%) marker chromosomes, three (0.14%) inversions and one (0.05%) duplication. Frequency of anomalies in men and women were similar: 42 and 40 cases respectively. CONCLUSIONS: Partners of infertile couples requiring IVF or ICSI treatment appear to be affected by higher frequency of chromosomal rearrangements than the general population. Categories with greater risk were represented by men with sperm cell count <20 x 10(6) sperm/ml, and women with history of pregnancy loss.

Influence of cigarette smoking on vitamin E, vitamin A, beta-carotene and lycopene concentrations in human pre-ovulatory follicular fluid.

Increasing evidence suggests that fat soluble vitamins and micronutrients have the potential for local modulation of follicular development. Cigarette smoking has been associated with accelerated follicular depletion and derangement of reproductive functions. The present study was initiated to investigate the impact of cigarette smoking on follicular and plasma concentrations of vitamin A, vitamin E, lycopene and beta-carotene. Samples were collected from 17 smokers and 43 non-smoking women undergoing assisted reproduction techniques. Assays were carried out by a reverse-phase high-pressure liquid chromatography (HPLC) method. Smokers had significantly (P < 0.05) lower levels of follicular fluid beta-carotene in comparison to non-smokers (0.02 +/- 0.02 vs. 0.09 +/- 0.02, respectively). No other significant influences on follicular and plasma concentrations were noted. Smokers showed a significantly (P < 0.05) lower fertilization rate in comparison to non-smokers, (55.9 % vs. 71.5 % , respectively). It is postulated that follicular depletion of the antioxidant beta-carotene occurs in response to oxidative stress imposed by cigarette smoke.

The soluble guanylate cyclase inhibitor methylene blue evokes preterm delivery and fetal growth restriction in a mouse model.

BACKGROUND: The present study was undertaken to test whether methylene blue a soluble guanylate cyclase inhibitor, can initiate delivery in the mouse. The potential adverse effects of methylene blue on the fetal growth process were also investigated. MATERIALS AND METHODS: ICR (CD-I) mice were injected subcutaneously with Methylene blue at 0 (vehicle), 5, 30, 50, 60 or 85 mg/Kg on gestation days 15.5 and 16 (plug day = gestation day 0). RESULTS: Methylene blue caused the mice to deliver before gestation day 18 (term gestation). This response was observed in 45%, 50% and 83% of animals receiving Methylene blue at 50, 60 or 85 mg/Kg, respectively (p < 0.05 vs. controls). In a dose-dependent fashion, Methylene blue induced a statistically significant (p < 0.05) derangement of the fetal growth process. CONCLUSION: The present study provides the first evidence that exposure to Methylene blue during late gestation induces preterm delivery and fetal growth restriction. These findings seem to favour the idea that soluble guanylate cyclase and its catalytic product play a role in the control of myometrial contractility and fetal growth process.

Transplacental exposure to methylene blue initiates teratogenesis in the mouse: preliminary evidence for a mechanistic implication of cyclic GMP pathway disruption.

BACKGROUND: The vital dye methylene blue (MB) has been shown to be teratogenic when injected into the amnion in the second trimester. On the other hand, the teratogenic potential of transplacental exposure to MB has not been determined. METHODS: MB was administered subcutaneously to ICR (CD-1) mice at 0, 35, 50, 60, or 70 mg/kg on gestation day 8 (plug day = day 0). Teratological assessments were carried out at term gestation, on gestation day 18. Since MB inhibits soluble guanylate cyclase enzyme activity, zaprinast (ZPN), a selective cGMP-phosphodiesterase type V inhibitor, was administered to prevent developmental disorders initiated by MB at 50 mg/kg. RESULTS: There was a dose-dependent increment of embryolethality. MB treatment also produced axial skeleton and neural tube defects. Coadministration of ZPN (20 mg/kg per three times) abolished completely MB-induced neural tube defects and reduced by one-half the incidence of fetuses exhibiting axial skeletal defects. ZPN did not provide protection against the embryocidal effects of MB. CONCLUSIONS: This study showed that transplacental exposure to MB is teratogenic in the mouse. Coadministration of ZPN prevented partly MB-induced teratogenesis, which supports the hypothesis that imbalance of cGMP pathway accounts, in part, for the teratogenicity of MB.

Antioxidant and GSH-related enzyme response to a single teratogenic exposure to the anticonvulsant phenytoin: temporospatial evaluation.

BACKGROUND: It has been proposed that the anticonvulsant drug phenytoin (PHT) requires bioactivation to reactive intermediate(s) to achieve its recognized teratogenic potential and that embryonal detoxification power may play a fundamental role in the teratogenic response. On this basis, we sought to investigate the potential effects of a teratogenic exposure to PHT on the activities of antioxidant and GSH-related detoxifying enzymes in gestational murine tissues. METHODS: Pregnant Swiss mice were injected intraperitoneally with 0 (vehicle) or 65 mg/kg of PHT on gestation day (GD) 12 (plug day = GD 1). Biochemical determinations, including activities of glutathione transferase, glutathione peroxidase, glutathione reductase, glyoxalase I, glyoxalase II, catalase, and superoxide dismutase, were carried out on maternal and embryonic/fetal livers and in placentas on GD 14 and 19. RESULTS: The major findings of this study show that (1) organogenesis-stage conceptal tissues have detectable levels of all the tested enzymes; (2) most of the embryonic liver and placental enzymes investigated undergo a significant induction within 48 hr (GD 14) after PHT administration; and (3) in the same tissues a down-regulation of enzyme activities is noted near term (GD 19). CONCLUSIONS: Overall, these findings show that teratogenic exposure to PHT is associated with a modulation of reactive-intermediates-scavenging enzyme activities, and provide further support for role of generation of reactive intermediates in PHT-induced teratogenesis.

Inhibition of nitric oxide synthesis causes preterm delivery in the mouse.

The aim of the present study was to investigate whether an inhibitor of nitric oxide (NO) synthesis provokes preterm delivery in a mouse model. ICR (CD-1) mice were injected s.c. with N(G)-nitro-L-arginine methyl esther (L-NAME) at 0, 40, 70 or 100 mg/kg on gestation day (GD) 15.5 and 16. Delivery was considered preterm if it occurred before GD 18. In a satellite study, the potential ability of the NO donor sodium nitroprusside (SNP) to prevent L-NAME-induced preterm delivery was tested. Five hours before the initiation of treatment regimen with L-NAME at 70 mg/kg, mice were implanted s.c. with micro-osmotic pumps infusing SNP at 0 or 10 microg/kg/min continuously for 3 days. Administration of L-NAME evoked preterm delivery. This response was noted in 64 and 60% of animals treated with 70 and 100 mg/kg L-NAME respectively (P < 0.05 versus control value). Infusion with SNP provided complete and significant (P < 0. 05 versus positive control value) protection from L-NAME-initiated preterm delivery. This is the first report to reveal that an inhibitor of NO synthesis initiates preterm delivery in a mouse model.

The influence of menopause and habitual smoking upon serum zinc, serum copper and the cardiovascular and immune parameters of women.

One hundred and thirty-three women in general good health were divided into two groups, according to menopausal status. The pre-menopausal group (n=106) was further subdivided into non-smokers (n=76) and smokers (n=30). All of the post-menopausal women were non-smokers (n=27). The determination of blood pressure (BP) and the collection of fasting blood samples were performed in the early morning hours. Habitual smoking increased the number of blood lymphocytes and monocytes in pre-menopausal women. The post-menopause group demonstrated an increase in BP, in serum cholesterol and triglycerides and a reduction of the serum zinc/copper (Zn/Cu) ratio. Serum Zn was positively correlated with serum glucose levels in the pre-menopausal group, regardless of smoking habit, but was negatively correlated in postmenopausal women. This may suggest that menopause induces changes in Zn metabolism and/or in insulin Serum Cu - particularly in smokers - was significantly correlated with blood lymphocytes. This may suggest an effect of smoking on the immune system via an alteration of Cu metabolism, including the synthesis and/or the release of ceruloplasmin, a known marker of inflammation. Moreover, serum Copper levels of both the pre- and the post-menopausal groups were significantly correlated with mean and diastolic B.P. while the serum Zn levels of the pre-menopausal group was significantly correlated solely with diastolic BP, implying that the metal plays a physiological role in some mechanism of blood pressure regulation. In the pre-menopausal non-smokers subgroup and the post-menopausal group, there was a weak, but statistically significant (p<0.01), correlation between systolic and mean BP, and blood lymphocytes levels. These data may be explained by a neuroendocrine influence, related partially to the morning hours.

Teratological interaction between the bis-triazole antifungal agent fluconazole and the anticonvulsant drug phenytoin.

Previous studies implicated the cytochrome P450 (CYP) system as critical in the teratogenic bioactivation of phenytoin (PHT). Fluconazole (FCZ) is an antifungal bis-triazole with potent inhibitory effect on the principal CYP-dependent metabolic pathway of PHT. In this study an in vivo experimental model was used to evaluate the potential ability of FCZ (2, 10, or 50 mg/kg intraperitoneally) to modulate PHT (65 mg/kg intraperitoneally) teratogenesis on day 12 (plug day = day 1) Swiss mice. PHT alone elicited embryocidal and malformative effects, with cleft palate as the major malformation. Pretreatment with the nonembryotoxic dosage of 10 mg FCZ/kg potentiated PHT-induced teratogenesis, as indicated by a twofold (from 6.2% to 13.3%) increment of cleft palate incidence (P < 0.05). Combined treatment with 50 mg FCZ/kg plus PHT resulted in a statistically significant (P < 0.05) increment of the resorption incidence recorded after PHT-alone exposure, but possibly as a consequence of the increased embryolethality, in the loss of the potentiative effect on PHT teratogenesis. Although the mechanistic nature of teratological interaction between FCZ and PHT remains to be established, these results may not support CYP system-mediated metabolic conversion as the mechanistic component of PHT teratogenesis.

[New aspects in the evaluation of risk factors for fetal development]. / Nuovi aspetti nella valutazione di fattori di rischio per lo sviluppo embrionale.

Much knowledge concerning the effects of xenobiotics on prenatal development derive from experimental studies, which are generally performed on laboratory animals according to standardized protocols. Conventional in vivo studies should be integrated by other models within a scientifically-based risk assessment strategy. The paper reviews a few in vitro and/or in vivo approaches: identification of critical effects through the characterization of the pathogenesis as well as the use of dose-response relationships; alternative models to identify reproductive risks from single substances and/or mixtures present in the environment; interactions between in vitro and in vivo studies in the risk assessment of solvents: embryonic metabolism in teratogenicity; interactions between experimental and epidemiological studies to understand the pathogenesis of embryolethality; risk assessment of the effects of prenatal exposure to ionizing radiations.

Aspirin pretreatment potentiates hyperthermia-induced teratogenesis in the mouse.

OBJECTIVE: Our purpose was to investigate the effect of aspirin pretreatment on hyperthermia-induced teratogenesis. The rationale for the study was based on the growing evidence that prostaglandin pathway may be involved in the cellular response to the thermic injury. STUDY DESIGN: On gestation day 8.5 Swiss mice were treated with 0 or 200 mg/kg of aspirin and 1 hour later exposed to a single 10-minute thermostatic bath treatment at 38 degrees C, 41 degrees C, 42 degrees C, or 43 degrees C. On gestation day 18 uterine contents were evaluated for developmental disorders, including prenatal mortality, intrauterine growth restriction, and external, visceral, and skeletal abnormalities. RESULTS: Consistent with expectations, hyperthermia impaired morphogenesis in a dose-related manner. Although aspirin alone did not reveal embryotoxicity, its administration potentiated hyperthermia-induced teratogenesis. A statistically significant interaction (p < 0.05) was observed at 42 degrees C, where the incidence of fetuses per litter with axial skeletal malformations increased from 20.3% to 55.7%. CONCLUSION: A nonteratogenic dose of aspirin enhanced the teratogenic response to hyperthermia. This result fits the hypothesis that prostaglandins may play a protective role in hyperthermia-induced teratogenesis.

Uterine artery Doppler velocimetry in pregnant women with lateral placentas.

The aim of this study was to compare the efficacy of placental, non-placental, mean of both uterine arteries Doppler velocimetry at 22-24 weeks gestation in the prediction of pregnancy induced hypertension (PIH) and intrauterine growth retardation (IUGR). Flow velocity waveforms were obtained by means of color and pulsed Doppler in 481 patients with lateral placentas at 22-24 weeks gestation. Placental location was determined by real time ultrasonography. Comparisons were performed between controls and pregnancies complicated by PIH and IUGR. Sensitivities, false positive rates and positive predictive values for PIH and IUGR of resistance indices (RI) above the 90th percentile, and diastolic notches in placental, non-placental or both uterine arteries were calculated. A mean uterine artery RI > or = 0.66 (90th centile) had better sensitivity than the placental (26.8% vs 17.1% for IUGR and 41.7% vs 33.3% for PIH) and the non-placental uterine artery (26.8% vs 21.9% for IUGR and 41.7% vs 33.3% for PIH). The presence of a diastolic notch in the placental uterine artery increased sensitivity (31.7% for IUGR and 50.0% for PIH) and positive predictive value of the test. In patients with laterally implanted placentas a mean of both uterine arteries RI above the 90th centile and the presence of a diastolic notch in the placental uterine artery at 22-24 weeks have a higher predictive value for the subsequent development of PIH and IUGR than the separate evaluation of the 2 uterine arteries.

Cardiotocographic and Doppler velocimetric patterns, pre- and post-thoracentesis, in a case of fetal hydrothorax.

Fetal hydrothorax is associated with elevated perinatal mortality. Management of this condition is controversial given that in utero spontaneous resolution has been described. A case of fetal hydrothorax associated with an extralobar lung sequestration that showed pathologic cardiotocographic patterns and abnormal Doppler velocimetry indices in several fetal vascular beds in reported. All pathologic patterns improved after fetal thoracentesis. It can be concluded that monitoring fetal well-being by means of cardiotocography and Doppler velocimetry may help in timing thoracentesis in cases of fetal hydrothorax.