Article

Low-dose aspirin and omega-3 fatty acids improve uterine artery blood flow velocity in women with recurrent miscarriage due to impaired uterine perfusion

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

To determine the effect of different therapeutic approaches on uterine artery blood flow in women with recurrent miscarriage (RM) and impaired uterine perfusion. Prospective, randomized study. Department of Obstetrics and Gynecology, University of Rome "Tor Vergata," Italy. Sixty women with unexplained RM and impaired uterine perfusion. Patients were randomly assigned to three different therapeutic regimens: 20 patients received a daily dose of 100 mg of aspirin (LDA); 20 patients were treated with omega-3 fatty acids (Omega(3)), 4 g daily; and 20 patients received LDA plus Omega(3). Doppler measurement of uterine artery pulsatility index (PI) was performed, in the midluteal phase of the cycle, before and after 2 months of therapy. All therapeutic regimens induced an improvement in uterine perfusion with a significant reduction of uterine artery PI values. LDA alone or in combination with Omega(3) was found to achieve the highest improvement of uterine blood flow. Omega-3 supplementation was less effective, as reflected by the lower PI values. LDA and Omega(3) are effective in improving uterine artery blood flow velocity in women with RM due to abnormal uterine perfusion. Further studies are needed to determine whether the improvement of uterine perfusion may lead to a better pregnancy outcome.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... The results have shown that uterine blood flow resistance is higher during the mid-luteal phase in women with recurrent abortions in comparison with normal women (3)(4)(5). Doppler ultrasound with an assessment of the pulsatility index (PI) as a value reflecting downstream resistance to blood flow has become widely accepted when monitoring high risk pregnancy. A relationship between increased impedance in uterine artery and poor pregnancy outcome has been reported by several studies (6)(7)(8). ...
... A study conducted by Lazzarin and colleagues on 60 women with the history of recurrent spontaneous miscarriages concerning prescribing aspirin per se or plus omega 3 showed significant improved uterine blood flow leading to decreased spontaneous abortion rates due to impaired uterine perfusion (4). It has also been reported that prescribing aspirin in conjunction with heparin decreased significantly spontaneous abortion during the first trimester of pregnancy, but the study did not show how aspirin in conjunction with heparin worked to lead to this result. ...
... The sample size was calculated based on a similar study with considering type1 error 0.05 and second type error 20%, d= 0.35 (4). According to the study design and estimation of 20% loss to follow up, the sample size in each group of samples obtained 30. ...
Article
Full-text available
Background Recurrent spontaneous abortion has high incidence rate. The etiology is unknown in 30-40%. However high uterine artery resistance is accounted as one of the recurrent abortion reasons. Objective The objective of the current study was to determine the impacts of vitamin E and aspirin on the uterine artery blood flow in women having recurrent abortions due to impaired uterine blood flow. Materials and Methods This randomized clinical trial was conducted on 99 women having uterine pulsatility index (PI) more than 2.5 and the history of more than two times abortions. The candidates were categorized into three groups; receiving aspirin, only vitamin E, and aspirin+vitamin E. After 2 months, uterine PIs were compared with each other. Results All drug regimens caused an enhancement in uterine perfusion with a significant decline in uterine artery PI value. The women receiving vitamin E in accompanied with aspirin had the least mean PI of the uterine artery (p<0.001). The total average PI score of the right and left uterine arteries in groups receiving vitamin E in accompanied with aspirin was lower than the two counterparts significantly (p<0.001). Conclusion Vitamin E, aspirin and especially their combination are effective in improving uterine artery blood flow in women with recurrent abortion due to impaired uterine blood flow. More well-designed studies are needed to find out whether the enhancement of uterine perfusion may lead to a better pregnancy outcome.
... The results reported in Alvarez et al. indicated that there was a moderate association between omega-3 intake and anxiety symptoms in pregnancy [38]. In some studies, omega-3 have been associated with increased uterine blood flow [39,40], which may lead to improved sexual function [41]. ...
... Various mechanisms have been proposed to explain the above findings, including improved blood flow in the body [39] especially in the pelvic organs, which can also lead to improved sexual function [41]. In a study on women with breast cancer, 6-month omega-3 intake significantly reduced vaginal atrophy and dryness by altering lactobacilli, cell maturation, and pH [58], which could be explained by increased pelvic blood flow. ...
Article
Full-text available
The aim of this study was to evaluate the effect of omega-3 fatty acid supplementation on female sexual function during pregnancy. The present study was a double-blind randomized controlled clinical trial performed on 124 pregnant women (62 people in each group) at 16–22 weeks of gestation who referred to health centers in Ilam in 2020 to receive prenatal care. The intervention group received 300 mg of omega-3 supplements and the control group received placebo once a day for 8 weeks. Data collection tools in this study included a demographic questionnaire, three 24-h dietary recall (24HR), female sexual function index (FSFI), and Van den Bergh Pregnancy-Related Anxiety Questionnaire (PRAQ). Before intervention, the total score of sexual function in the intervention group and control groups, showed no statistically significant difference (P = 0.123). However, 4 and 8 weeks after intervention, the mean total score of sexual function in the intervention group was significantly higher than that of the control group after intervention (P < 0.0001). Before intervention, the total score of gestational anxiety in the intervention and control groups, showed no statistically significant difference (P = 0.149). However, 4 and 8 weeks after intervention, the mean total score of gestational anxiety in the intervention group was significantly lower than that of the control group (P < 0.0001). Based on three 24-h dietary recall, regardless of daily intake of 300 mg of omega-3 supplement, the percentage of polyunsaturated fatty acid (PUFA) intake from daily energy intake was not statistically significant between the intervention and control groups from baseline to follow-up (P > 0.01). Based on the results of this study, omega-3 supplementation could improve sexual function in pregnant women by preventing increased pregnancy anxiety. However, more studies are needed to prove the effectiveness of omega-3s on female sexual function during pregnancy. This study was approved by the Ethics Committee of Ahvaz Jundishapur University of Medical Sciences (Ref. ID: IR.AJUMS.REC.1398.935) and registered in Iranian Registry of Clinical Trials (Ref. ID: IRCT20200415047078N1).
... Therefore, it is recommended to consume EPA and DHA through the diet. DHA plays an important role in the function and responsiveness of cell membranes, tissue metabolism and hormonal and other signaling pathways [4,5]. It also constitutes the major fatty acid in the brain and retina [6]. ...
... Two different pathways exist for PUFA synthesis: the oxygen-dependent aerobic fatty acid synthase pathway (FAS), also known as elongase-desaturase pathway, and the oxygen-independent anerobic polyketide synthase pathway (PKS)-also designated as the PUFA synthase pathway [45]. In the FAS pathway, the starting point for PUFA synthesis is C18:3-9,12,15, which is converted by ∆6 desaturase into C18:4-6,9,12,15 and by elongase into C20: [4][5][6][7][8]11,14,17. The latter is then converted into C20: 8,11,14,17 by ∆5 desaturase, followed by elongation to 22:5-7,10,13,16,19 and, finally, conversion into DHA (22:6-4,7,10,13,16,19) by ∆4 desaturase [43,[45][46][47]. ...
Article
Full-text available
Thraustochytrids are considered natural producers of omega-3 fatty acids as they can synthesize up to 70% docosahexaenoic acids (DHA) of total lipids. However, commercial and sustainable production of microbial DHA is limited by elevated cost of carbon substrates for thraustochytrids cultivation. This problem can be addressed by utilizing low-cost renewable substrates. In the present study, growth, lipid accumulation and fatty acid profiles of the marine thraustochytrid Aurantiochytrium sp. T66 (ATCC-PRA-276) cultivated on volatile fatty acids (C1, formic acid; C2, acetic acid; C3, propionic acid; C4, butyric acid; C5, valeric acid and C6, caproic acid) and glucose as control were evaluated for the first time. This strain showed an inability to utilize C3, C5 and C6 as a substrate when provided at >2 g/L, while efficiently utilizing C2 and C4 up to 40 g/L. The highest cell dry weight (12.35 g/L) and total lipid concentration (6.59 g/L) were attained when this strain was cultivated on 40 g/L of butyric acid, followed by cultivation on glucose (11.87 g/L and 5.34 g/L, respectively) and acetic acid (8.70 g/L and 3.43 g/L, respectively). With 40 g/L butyric acid, the maximum docosahexaenoic acid content was 2.81 g/L, corresponding to 42.63% w/w of total lipids and a yield of 0.23 g/gcell dry weight (CDW). This marine oleaginous microorganism showed an elevated potential for polyunsaturated fatty acids production at higher acetic and butyric acid concentrations than previously reported. Moreover, fluorescence microscopy revealed that growth on butyric acid caused cell size to increase to 45 µm, one of the largest values reported for oleaginous microorganisms, as well as the presence of numerous tiny lipid droplets.
... This outcome is encouraging and interesting because it allows reasoning about the role played by omega as antioxidant and in reducing inflammatory processes to facilitate placentation and to enable good placental flow for proper fetal growth [1,20]. Such omega performance has been investigated and cited in several studies [21][22][23]. According to a study conducted in Egypt in 2016, omega has successfully increased the amount of amniotic fluid in patients presenting unexplained oligohydramnios. ...
... The aforementioned study has also found reduced uterine artery resistance and pulsatility indices; this outcome suggested that the increased amniotic fluid was associated with improved uterine flow [21]. Other studies have also proved that omega improved uterine artery perfusion in non-pregnant patients [22]. Importantly, animal models treated with heparin also recorded reduced uterine artery resistance and pulsatility indices [23]. ...
... Interestingly, dietary supplementation, such as omega-3s, might mitigate IR associated inflammation. Omega-3s, such as docosahaexanoic (DHA), exert anti-inflammatory effects including 70 reduced cytokine, prostaglandin, and eicosanoid production in humans [18][19][20]. Dietary DHA is also readily incorporated into equine and porcine [21][22][23] endometrium and can alter porcine milk composition [23], indicating that dietary DHA can be utilized. ...
... Thus far, studies have investigated the systemic influence of EMS [5,41], impacts on reproductive cyclicity and follicular dynamics [4,6], or involvement in laminitis [14,15,42,43]. Dietary supplementation of omega-3s provides an option for treatment to mitigate IR effects through reducing pro-inflammatory secretion [18][19][20]. 190 ...
Article
Full-text available
Insulin resistance (IR) is characterized by an increase in biomarkers of systemic inflammation and susceptibility to laminitis in horses. Impacts on reproduction include a lengthened interovulatory period in horses. Dietary omega-3 (docosahexaenoic acid [DHA]) promotes anti-inflammatory processes, has been implicated in health benefits, and can reduce cytokine secretion. This preliminary study investigated the impact of IR as well as the influence of dietary supplementation (DHA) on the uterine fluid proteome in early pregnant horses. Mares were artificially inseminated; uterine fluid and embryos were collected on d 12.5 after ovulation. Uterine fluid was pooled for metabolic and diet categories (n = 8; n = 2 per metabolic and dietary status) and concentrated, and the proteome was analyzed using tandem mass spectrometry (iTRAQ). Five proteins met differential abundance criteria (±1.5-fold change, P < .05) in all comparisons (Control C, IS vs. C, IR; C, IS vs. DHA, IS; C, IR vs. DHA, IR). Serum amyloid A, afamin, and serotransferrin were upregulated in C, IR mares but downregulated in DHA, IR mares when compared to C, IS and C, IR, respectively. Quantitative PCR supported mass spectrometry results. The presence of serum amyloid A and serotransferrin in histotroph of IR mares potentially indicates an inflammatory response not seen in IS counterparts. These preliminary findings provide novel evidence on the potential impact of insulin resistance and DHA supplementation on the secreted equine uterine proteome during early pregnancy.
... Omega-3 can influence reproductive processes by acting as precursors for prostaglandin synthesisaswell; omega-3 can modulate the expression of many enzymes involved in prostaglandin and steroid metabolism which are found to be necessary for both ovarian and uterine function and seem to be essential in any successful reproductive procedure [22][23][24][25] . This study aims to investigate the possible effect of preconceiving supplementation of omega-3 PUFAs on intracytoplasmic sperm injection outcomes on the basis of the ratio between the follicles and retrieved oocytes, the rate of fertilization, and quality of the embryo. ...
Article
Full-text available
This study aims to evaluate the role of preconceiving omega 3 polyunsaturated fatty acids supplementation in enhancing the proportion between follicles and retrieved ova, the fertilization rate, and the embryonic grading in subfertile females experiencing intracytoplasmic sperm injection management protocols. One-hundred twenty subfertile women aged 20-40 years-old undergoing intra-cytoplasmic sperm injection were recruited in this randomized double-blinded placebo-controlled clinical trial, at at Fertility Center/ Al-Sadr Teaching Hospital/ Al Najaf/ Iraq. They were randomly assigned into two groups; group A (omega-3) includes 60 subfertile women who received one capsule 1000mg omega-3 and Group B (placebo) includes 60 subfertile women who received a placebo contain Liquid Paraffin 500mg for eight weeks. The number of follicles, number of oocytes, fertilization rates, and embryonic quality were recorded in both groups. The study result revealed that the ratio of follicle/retrieved oocyte, the number of metaphase II oocytes, fertilization rate, and grade I embryo were more in the group A compared to group B. Supplementation with Omega-3 polyunsaturated fatty acids can increase the ratio of follicle/retrieved oocyte, the number of metaphase II oocytes, fertilization rate, and grade I embryo, and thereby improving the pregnancy outcome in intracytoplasmic sperm injection cycles. © 2018 Oriental Scientific Publishing Company. Ltd.All Rights Reserved.
... Besides choline and inositol, essential fatty acids, such as omega (ω)-3 and 6, are often found in culture media. They are metabolized to form eicosanoids that affect lipid homeostatic processes as well as the inflammatory response [60][61][62][63]. These lipids usually bind to albumin, and can be supplemented to cells through albumin without notice. ...
Article
Full-text available
Stem cells can differentiate to diverse cell types in our body, and they hold great promises in both basic research and clinical therapies. For specific stem cell types, distinctive nutritional and signaling components are required to maintain the proliferation capacity and differentiation potential in cell culture. Various vitamins play essential roles in stem cell culture to modulate cell survival, proliferation and differentiation. Besides their common nutritional functions, specific vitamins are recently shown to modulate signal transduction and epigenetics. In this article, we will first review classical vitamin functions in both somatic and stem cell cultures. We will then focus on how stem cells could be modulated by vitamins beyond their nutritional roles. We believe that a better understanding of vitamin functions will significantly benefit stem cell research, and help realize their potentials in regenerative medicine.
... In conclusion our results can be considered as a sign for a significant endometrial contribution as derivation of blood flow impedance to unexplained group. Mid-luteal or peri-implantation period Doppler measurements should be considered in infertility patients and if impedance to uterine vasculature is found to be high these patients may become candidates for therapies increasing the luteal blood low like aspirin and omega 3 in unexplained infertility and IVF patients (16,17). Embryo freezing and subsequent hormonal preparation of endometrium can be considered. ...
Article
Full-text available
Uterine perfusion, particularly the endometrial blood flow, may have an important role in endometrial receptivity. In order to assess the contribution of sub endometrial blood flow in the etiopathogenesis of unexplained infertility mid luteal- peri-implantation period spiral artery transvaginal color Doppler parameters were measured and compared with fertile controls. Forty-two consecutive patients admitted to Izmir Katip Celebi University Ataturk Training and Research Hospital, Department of Obstetric and Gynecology with the diagnosis of unexplained infertility after standard diagnostic work up constituted the study group and they were compared with a fertile control group admitted to hospital with non specific gynecological complaints or for check-up in the same period. Mid luteal transvaginal color Doppler ultrasonography was applied to each patient by the same radiologist who was blind to the diagnosis of the particular patient and, RI (resistance index) and PI (pulsatility index) values were calculated. There were no significant differences between the two groups, in respect to age, body mass index, basal hormonal and mid luteal progesterone levels (p>0.05). For the fertile control group, mid luteal-peri-implantation phase endometrial spiral artery mean RI values were calculated as 0.48±0.08 SD and mean PI values as 0.65±0.18 SD. For the study group, mean RI values were calculated as 0.54±0.07 SD, PI values were calculated as 0.80±0.16 SD. The differences for RI (p=0.009) and PI (p=0.004) were statistically significant. According to Doppler parameters, unexplained infertility patients have high impedance blood flow in spiral arteries which means that peri-implantation blood flow in these patient is lower than fertile controls. These findings suggest that endometrial perfusion may have an important contribution to etiopathogenesis of unexplained infertility.
... [128] Aspirin helps in improving uterine perfusion. [129] Aspirin is useful in many undiagnosed implantation failure patients. However, in the absence of strong evidence, routine use of Aspirin is not recommended (Evidence level II) • Progesterone: Meta-analysis of 4 randomized trials and only 132 women in total showed a statistically significant reduction in miscarriages. ...
Article
Full-text available
Recurrent miscarriages are postimplantation failures in natural conception; they are also termed as habitual abortions or recurrent pregnancy losses. Recurrent pregnancy loss is disheartening to the couple and to the treating clinician. There has been a wide range of research from aetiology to management of recurrent pregnancy loss. It is one of the most debated topic among clinicians and academics. The ideal management is unanswered. This review is aimed to produce an evidence‑based guidance on clinical management of recurrent miscarriage. The review is structured to be clinically relevant. We have searched electronic databases (PubMed and Embase) using different key words. We have combined the searches and arranged them with the hierarchy of evidences. We have critically appraised the evidence to produce a concise answer for clinical practice. We have graded the evidence from level I to V on which these recommendations are based. KEY WORDS: Aspirin, antiphospholipids syndrome, immunotherapy, low molecular weight heparin, recurrent pregnancy loss, recurrent miscarriage, unexplained to generate most relevant results. The evidence was searched using individual subclass of etiology of recurrent pregnancy loss. Different key words were used such as recurrent miscarriage, recurrent pregnancy loss, habitual abortions, pregnancy failures, unexplained, and idiopathic miscarriage; and these words were combined with various factors known to cause or treat miscarriages. The search results were combined and most relevant results were grouped together for critical appraisal.
... Omega-3 can influence reproductive processes by acting as precursors for prostaglandin synthesisaswell; omega-3 can modulate the expression of many enzymes involved in prostaglandin and steroid metabolism which are found to be necessary for both ovarian and uterine function and seem to be essential in any successful reproductive procedure [22][23][24][25] . This study aims to investigate the possible effect of preconceiving supplementation of omega-3 PUFAs on intracytoplasmic sperm injection outcomes on the basis of the ratio between the follicles and retrieved oocytes, the rate of fertilization, and quality of the embryo. ...
Article
Full-text available
This study aims to evaluate the role of preconceiving omega 3 polyunsaturated fatty acids supplementation in enhancing the proportion between follicles and retrieved ova, the fertilization rate, and the embryonic grading in subfertile females experiencing intracytoplasmic sperm injection management protocols. One-hundred twenty subfertile women aged 20-40 years-old undergoing intra-cytoplasmic sperm injection were recruited in this randomized double-blinded placebo-controlled clinical trial, at at Fertility Center/ Al-Sadr Teaching Hospital/ Al Najaf/ Iraq. They were randomly assigned into two groups; group A (omega-3) includes 60 subfertile women who received one capsule 1000mg omega-3 and Group B (placebo) includes 60 subfertile women who received a placebo contain Liquid Paraffin 500mg for eight weeks. The number of follicles, number of oocytes, fertilization rates, and embryonic quality were recorded in both groups. The study result revealed that the ratio of follicle/retrieved oocyte, the number of metaphase II oocytes, fertilization rate, and grade I embryo were more in the group A compared to group B. Supplementation with Omega-3 polyunsaturated fatty acids can increase the ratio of follicle/retrieved oocyte, the number of metaphase II oocytes, fertilization rate, and grade I embryo, and thereby improving the pregnancy outcome in intracytoplasmic sperm injection cycles. Keywords: Omega-3, Fertilization Rate, Intracytoplasmic Sperm Injection, Retrieved ova,Subfertile women, Metaphase II oocytes.
... Omega-3 can influence reproductive processes by acting as precursors for prostaglandin synthesisaswell; omega-3 can modulate the expression of many enzymes involved in prostaglandin and steroid metabolism which are found to be necessary for both ovarian and uterine function and seem to be essential in any successful reproductive procedure [22][23][24][25] . This study aims to investigate the possible effect of preconceiving supplementation of omega-3 PUFAs on intracytoplasmic sperm injection outcomes on the basis of the ratio between the follicles and retrieved oocytes, the rate of fertilization, and quality of the embryo. ...
... This is in accordance with the ASPRE study [19] and a study from 2010, where Bujold et al. [9] evaluated clinical data on lowto mid-dose aspirin using meta-analysis, and showed that when the women started treatment on or before week 16, the risk of having PE or IUGR was significantly lowered compared to those who started aspirin administration after week 16. Furthermore, several clinical studies have shown that low-dose aspirin reduces uteroplacental vascular impedance in gestation [10,20]. ...
Article
Full-text available
Objective: The objective of this study was to understand the effect of acetylsalicylic acid (aspirin) on resistance arteries from mesentery and uterus. During pregnancy, the uterine vasculature undergoes consistent growth to provide sufficient uteroplacental blood flow, a process whose failure is associated with pregnancy complications characterized by high uterine vascular resistance. Methods: Uterine arcuate (UA) and mesenteric arteries (MA; diameter <300 µm) isolated from non-gravid, mid-gravid (day 14), and late-gravid rats (day 20) were exposed to aspirin (10⁻¹² to 10⁻⁵ M). Further, in UA from late-gravid rats, aspirin was evaluated in presence of inhibitors of nitric oxide synthases, cyclooxygenase, cyclic nucleotides (cAMP, cGMP) and BK channels, and also on endothelium-denuded vessels. Results: Aspirin dilated both UA and MA in a dose dependent manner. Pregnancy increased aspirin vasodilation in MA and UA from mid-gravid rats, an effect that was reduced in vessels from late gravid animals at concentrations >10⁻⁷ M. Further, uterine vasodilation was significantly reduced when the endothelium was removed (p < 0.001), and by inhibitors of nitric oxide synthase (p < 0.001), cyclooxygenase synthase (p < 0.05), cyclic nucleotides cGMP/cAMP and BK channels. Conclusion: This is the first study to show a direct vasodilatory effect of aspirin on rat uterine artery that is mediated by a combination of cellular – primarily endothelial - mechanisms. Our results in UA suggest that the use of aspirin may be effective in enhancing uteroplacental blood flow, while its vasodilation effect on MA may lower peripheral resistance.
... Subsequently, Lazzarine and his colleagues conducted a study on 60 women with unexplained RPL and impaired uterine perfusion to determine the effect of different therapeutic approaches on uterine artery PI. 19 Patients were randomly assigned to three different therapeutic regimens; 20 patients received a daily dose of 100 mg (low dose) of aspirin (LDA); 20 patients were treated with omega-3-fatty acids 4 mg daily, and 20 patients received LDA and omega-3-fatty acids together. They found that all therapeutic regimens induced an improvement in uterine perfusion with a significant reduction in uterine artery PI values. ...
Article
Full-text available
Objective: To evaluate uterine artery blood flow during the mid-luteal phase in women with recurrent pregnancy loss (RPL), and compare to normal fertile controls.\nMaterial and Methods: Sixty-two non-pregnant patients with a history of two or more consecutive spontaneous abortions, and 30 women with a history of at least one pregnancy without any complications were evaluated as the study group, and the control group, respectively. Among the 62 patients with RPL, 32 were classified as “primary aborters” due to the absence of previous live births, whereas 30 were considered as “secondary aborters,” due to having had at least one previous live birth followed by two or more consecutive pregnancy losses. Transvaginal 3D power Doppler ultrasonography was performed to all patients in the second phase of non-pregnant unstimulated cycle to detect uterine arterial pulsatility index (PI). The indices between the two groups were compared.\nResults: The left and right uterine arterial PI values found in the study subgroups were statistically significantly higher than those in the control group (Primary RPL; right PI: 2.81 ± 0.69, left PI: 2.72 ± 0.61, p< 0.001; secondary RPL; right PI: 2.63 ± 0.59, left PI: 2.6 ± 0.57, p<0.001). When all patients with RPL in the study group were evaluated according to their etiologic factors, 3 groups were sufficient for statistical analysis; patients with hereditary thrombophilia, anatomical abnormalities, and unexplained etiology. All these groups had uterine PI values higher than the control group in both left and right uterine arteries. Endometrial thickness was found significantly lower in both primary and secondary aborters than that in the control group (11.2±2.5, 9.7±2.9 and 9.5±3.1, respectively). No significant correlation was found between the mid-luteal progesterone and estradiol levels, and endometrial thickness, and PI and resistance index (RI) values (p>0.05).\nConclusions: The presence of good uterine blood flow is an important prerequisite for successful pregnancy, as higher uterine artery blood flow resistance was shown in RPL. Increased resistance to uterine blood flow may be an important contributing factor to some causes of RPL and may represent an independent factor for the risk of pregnancy loss.
... Hay numerosos trabajos de investigación en curso que pretenden responder la incógnita de los abortos recurrentes idiopáticos, con líneas tan interesantes como el déficit de expresión de moléculas necesarias para la implantación a nivel endometrial (62) y la disminución en la perfusión uterina peri y post implantación (63). El problema principal que plantean los grupos estudiados es la dificultad en seleccionar pacientes que compartan similares condiciones y la alta tasa de éxito espontáneo en las pacientes con aborto recurrente idiopático (50-60%), lo que hace -Los otros estudios de abortadora primaria aplican por igual. ...
Article
Full-text available
Aproximadamente 1–3% de parejas en edad reproductiva experimentan 3 ó más abortos espontáneos consecutivos, lo que se define como aborto recurrente. La evaluación debe incluir una detallada historia clínica y examen físico, seguida de una serie de exámenes protocolizados destinados a detectar los factores más frecuentemente involucrados en esta patología (anatómico, cromosómico, inmunológico, endocrinológico y trombofílico). El manejo debe basarse en evidencias, evitando tratamientos experimentales o sin sustento científico, e incluyendo siempre un adecuado soporte emocional, tan necesario en estas parejas. A pesar de los esfuerzos por dilucidar los orígenes del aborto recurrente, sigue existiendo un 50% de casos sin causa aparente, los cuales suelen lograr tasas de embarazo exitoso de hasta 70% sin mediar tratamiento médico alguno.
... Lower RI and PI are associated with lower impedance to uterine artery blood flow, which leads to a greater blood flow to the endometrium. The anticoagulant drug aspirin has a vasodilatory effect (35) and suppresses the formation of thromboxane A without affecting prostaglandin I2 (�6). This may explain the reduction in PI and RI observed more significantly with the combination therapy than with estrogen-only therapy. ...
Article
Full-text available
Intrauterine adhesion (IUA) is one of the most common gynecological diseases in women of reproductive age. IUA, particularlyin moderate to severe forms, accounts for a large percentage of infertility cases. Clinically, the first‑line treatment strategy for IUA is transcervical resection of adhesion (TCRA), followed by adjuvant postoperative treatment. Estrogen is one of the classic chemotherapies used following TCRA and contributes to preventing re‑adhesion following surgery. However, estrogen has limited effects in promoting pregnancy, which is the ultimate goal for IUA management. In the present study, a transdermal estrogen gel and oral aspirin combination therapy was used in patients with IUA following TCRA. Compared with in the control group (transdermal estrogen only therapy), the combination therapy significantly increased endometrial receptivity marker (αvβ3 and laminin) expression in endometrium tissues. Additionally, ultrasonic examination revealed the pulsatility index and resistant index of the uterine artery were lower in the combination therapy group. Combination therapy promoted angiogenesis and prevented fibrosis following TCRA more effectively than estrogen‑only therapy. Collectively, the evaluation indices, including American Fertility Society score, endometrial parameters and pregnancy rate, indicated that patients with combination therapy had better prognoses in endometrial repair and pregnancy. In conclusion, postoperative combination therapy with transdermal estrogen gel and oral aspirin may be more efficacious in enhancing endometrial receptivity by increasing uterine blood and angiogenesis, contributing to improved fertility prognosis. The findings of the present study may provide novel guidance to the clinical treatment of IUA.
... Conclusively, data available so far on human and animal investigations suggest that supplementation of omega-3-fatty acids in male [27][28][29] as well female individuals [16,[19][20] improves reproductive success. Therefore, an omega-3-fatty acid supplementation as part of alimentary modification should be considered to improve female as well as male fertility in a multimodal approach. ...
... Analysis of the fatty acid profile revealed that subjects consuming the MD had a significantly higher level of DHA after the dietary intervention, whereas the CR group showed significantly lower concentrations of EPA and GLA. Both EPA and DHA are very important in the human diet as they regulate many essential metabolic processes, gene expression and build cell membranes in body structures (Conquer et al., 2000;Lazzarin et al., 2009;Smith et al., 2011). One of the most important roles of EPA and DHA includes the regulation of inflammatory processes. ...
Article
Full-text available
The aim of the study was to investigate the efficacy of 6 week Mediterranean diet or 30% calorie restriction on the fatty acid profile and eicosanoids (hydroxyoctadecadienoi acids and hydroxyeicosatetraenoic acids) concentration. Furthermore, basic biochemical variables such as insulin, glucose, HOMA-IR, and a lipid profile were estimated. The study enrolled 94 Caucasian former athletes aged 20-42, with body height of 179 ± 16.00 cm and body mass of 89.26 ± 13.25 kg who had not been active for at least 5 years. The subjects were randomly assigned to one of the three intervention groups: CR group – the 30% calorie restriction (n = 32), MD group - the Mediterranean diet (n = 34), and C group - a control group (n = 28). The pattern of nutrition was analysed before and after the experiment using the 72 h food diaries. In order to evaluate the effect of diet intervention, the following variables were measured: anthropometrics, basic biochemical variables (insulin, fasting glucose, HOMA-IR, lipid profile), fatty acids and their blood derivatives profiles. The CR group showed significantly lower levels of several biochemical variables, i.e., BMI, total cholesterol LDL, TG, total lipids, insulin and HOMA – IR (p < 0.05). Subjects consuming the MD diet significantly decreased their BMI and reduced the level of total lipids (p < 0.05). We did not find any significant changes in the C group. The analysis of the fatty acid profile revealed that the CR group had a significantly decreased EPA level (p < 0.05). The MD group showed a significantly increased level of the DHA (p < 0.05) and improvement in the omega - 3 index (p < 0.05). Subjects following the MD also showed significantly lower concentrations of 15 - hydroxyicosatetraenoic acid (15-HETE). We did not observe any significant differences between the CR and C groups. Within short time, calorie restriction helps to improve lipid variables and insulin resistance. The MD diet seems to be more advantageous in the decrease of inflammation, but does not improve basic biochemical variables. We can conclude that calorie restriction can be a good choice for former athletes, although EPA and DHA supplementation is needed.
... Previous studies provided evidence that low-dose aspirin as a common anticoagulant can produce a vasodilatory effect. 9 Supplementation with low-dose aspirin has been widely reported to be effective in improving uterine blood flow and pregnancy outcomes in patients with impaired uterine vascularization who had undergone assisted reproductive technologies. 10 Based on these observations, an attempt was made to evaluate differences in uterine artery blood flow parameters and pregnancy outcomes, if any. ...
Article
Objectives: The purpose of this study was to evaluate differences in uterine artery blood flow parameters and pregnancy outcomes, if any. An investigation was conducted to determine the effects of low-dose aspirin on uterine artery blood flow indices in patients with recurrent pregnancy loss. Methods: This observational study included 353 Chinese women with a history of recurrent pregnancy loss and 85 women without a history of recurrent pregnancy loss (control group) from Ren Ji Hospital. All patients were scanned transvaginally with transvaginal Doppler sonography 6 to 8 days after ovulation to measure the pulsatility index (PI), resistive index (RI), and systolic-to-diastolic ratio (S/D) of the left and right main uterine arteries. Low-dose aspirin at a dose of 50 mg/d was administered orally in patients with recurrent pregnancy loss for 2 months, and the blood flow indices were measured subsequently. The Student t test was used for analysis of the results, P < .05 was considered significant. Results: The mean PI and S/D of the uterine arteries in the recurrent pregnancy loss group were significantly higher than in the control group. Although not statistically significant, the RI was higher in the recurrent pregnancy loss group than the control group. Moreover, the PI and S/D increased as the number of pregnancy losses increased. Significant enhancements of the PI and S/D were observed in patients with 4 or more consecutive abortions. After low-dose aspirin supplementation, patients with recurrent pregnancy loss showed a highly significant reduction in the PI and S/D. Conclusions: Uterine blood flow decreased during the luteal phase in patients with recurrent pregnancy loss. Low-dose aspirin induced a reversible increase in uterine blood flow and may be of therapeutic value.
... Miscarriage occurs in 15-20% of all pregnancies, and some women who experience repeated miscarriages have an autoimmune condition that is known as antiphospholipid syndrome. Fish oil can prevent miscarriage in women with antiphospholipid antibody syndrome and a history of past miscarriage (Rossi and Costa, 1993;Lazzarin et al. 2009). Preterm births are linked to adverse outcomes for the infant, and there is some evidence that consuming fish oil or fish-derived omega-3 PUFAs during pregnancy can reduce the likelihood of preterm birth and increase the birth weight (Salvig et al. 2011). ...
... They concluded that LDA and 3 are effective in improving uterine artery blood flow velocity in women with RM due to abnormal uterine perfusion. Further studies are needed to determine whether the improvement of uterine perfusion may lead to a better pregnancy outcome [13]. ...
Article
Full-text available
Objective: To study the effect of prophylactic use of low dose aspirin and heparin on patients with recurrent unexplained pregnancy loss. Methods: Prospective case control study conducted on 180 pregnant women randomized into two equal groups. Group 1 received low-dose aspirin 75 mg and heparin 5000 IU subcutaneous every 12 h. Group 2 received no treatment. Results: There was a statistically significant difference between the two study groups regarding number of patients who completed their first trimester (66 versus 39) (p values 0.018). The outcome regarding completion of first trimester was not related to age, BMI or number of previous abortions in both the study groups. Complications of the use of aspirin calheparin occurred in 60% of the patients. The most common complication was bruising at injection site occurring in 60% of the patients followed by bleeding gums (14.4%), gastrointestinal troubles (12.2%), epistaxis (10%) and transient thrombocytopenia in only 2.22% of the patients (Table 4). Conclusion: The use of prophylactic dose of calheparin and aspirin is associated with increased chance of passing 1st trimester safely regardless the age, body mass index or number of abortion in women with unexplained recurrent spontaneous abortion.
... In addition, abnormal uterine and ovarian blood flow was associated with similar reproductive outcomes such as stillbirth (Singh et al. 2012), preeclampsia (Xu et al. 2015), and pregnancy loss (Koo et al. 2015;Mesdaghinia et al. 2017;Thilaganathan et al. 2010). Although the pathophysiological mechanisms surrounding pregnancy loss are not fully understood, LDA has been suggested as a potential treatment to reduce pregnancy loss based on commonly observed symptoms in women who have experienced loss, which include inflammation in the reproductive tract and abnormal uterine, endometrial, ovarian, and placental blood flow (Koo et al. 2015;Lazzarin et al. 2009;Mesdaghinia et al. 2017). Indeed, an association between preconception-initiated LDA and increased clinical pregnancy rates was suggested in women undergoing in vitro fertilization treatment (Ruopp et al. 2008). ...
Article
Inflammation has been linked to several complications in pregnancy, including pregnancy loss. Due to its anti-inflammatory properties, aspirin, a widely available and inexpensive therapy, has potential to help mitigate the negative effects of inflammation along the reproductive pathway. Therefore, the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was designed to elucidate whether preconception-initiated daily low-dose aspirin would increase the live birth rate in women with 1-2 prior pregnancy losses and no infertility diagnosis and attempting unassisted conception. Here, we present an overview of the collected findings. Low-dose aspirin was associated with an increased live birth rate among women with a single loss at <20 weeks gestation within the past year. When stratified by tertile of C-reactive protein (CRP), a biomarker of inflammation, treatment with aspirin restored a decrement in the live birth rate in women in the highest CRP tertile (relative risk 1.35, 95% confidence interval 1.08-1.67), increasing to similar rates as women of the lower and mid-CRP tertiles. The same effect modification by inflammation status was observed when examining the effect of low-dose aspirin on offspring sex ratio. These results suggest that inflammation plays an important role in reproduction, and that chronic, low-grade inflammation may be amenable to aspirin treatment.
... So, the authors suggested that these data should be considered of importance as specific therapeutic approaches improving the uterine perfusion may lead to better pregnancy outcome. So, in the completion of this previous work Lazzarin et al. [13] conducted a study on sixty women with unexplained RPL and impaired uterine perfusion to determine the effect of different therapeutic approaches on uterine artery PI in those women, patients were randomly assigned to three different therapeutic regimens; 20 patients received a daily dose of 100 mg of aspirin (LDA); 20 patients were treated with omega-3fatty acids 4 mg daily; and 20 patients received LDA and omega-3-fatty acids, they found that all therapeutic Study of uterine artery Doppler velocity waveforms in patients with recurrent early pregnancy loss Benha Journal Of Applied Sciences, Vol. (7) Issue (7) (2022( regimens induced an improvement in uterine perfusion with a significant reduction in uterine artery PI values. ...
... Previous data available in this field about RPL treatment was about low-dose aspirin (100 mg / day) alone or in association with Omega-3, which has been investigated in relation to uterine arteries flow indexes in non-pregnant women. It has been shown that this kind of treatments are able to improve the uterine perfusion with a reduction of the PI of the uterine arteries in the mid-luteal phase in patients with RPL [24]. LMWH effects, described from our results, could have important clinical applications in terms of ameliorating placental vascularization, but its use should be targeted according to VI value and ANA status to be effective. ...
Article
Full-text available
Background: The potential role of antinuclear antibodies (ANA) in recurrent pregnancy loss (RPL) pathogenesis is still debated, although some evidences suggest that they could affect pregnancy outcome, leading to a higher miscarriage rate in these patients. A hypothesized mechanism is through changes in uterine flow in pre-conceptional stage, by modifying endometrial receptivity in RPL. However, scant data are available, in pregnancy, about their role in RPL placental perfusion, also in relation to its potential treatments, such as low molecular weight heparin (LMWH). The aim of this study is to retrospectively further investigate the correlation between two-dimensional (2D) and three-dimensional (3D) uterine and placental flow indexes and the presence or the absence of ANA in women with unexplained RPL (uRPL), treated or not treated with LMWH. Methods: 2D Doppler measurement of pulsatility index (PI) of the uterine arteries and 3D ultrasonography determination of vascularization index (VI), flow index (FI) and vascularization flow index (VFI) was carried out with the aid of the virtual organ computer-aided analysis (VOCAL) technique in LMWH treated (n 24) and not treated-uRPL patients (n 20) and in the relative control group (n 27), each group divided in ANA+ and ANA- subgroups. Serum assay for the presence of ANA was performed in all women. Results: No differences were found in PI, VFI and VI values, by comparing the different groups. A difference in VI values was found for ANA- patients between RPL women not treated with LMWH and the treated ones (p = 0,01), which have lower VI values and similar to controls. By considering only ANA- treated and not treated RPL patients, the ROC curve shows an area of 0,80 and at the VI cut-off of 11,08 a sensitivity of 85% and a specificity of 67%. Conclusions: LMWH could exert a potential beneficial effect in restoring the physiological blood flow supply in terms of VI in uRPL ANA- status, suggesting to include ANA and VI investigations in the RPL diagnostic algorithm in a research context, since further studies are needed to clarify this challenging hypothesis in order to try to ameliorate ANA and abnormal placental vascularization negative influence on RPL pregnancy outcome .
... EPA and DHA, on the other hand, play critical roles in many parts of the human body, including cell membrane stability (Lazzarin et al., 2009), anti-inflammatory (Conquer et al., 2000;Smith et al., 2011), and are reported as precursors of several metabolites related to good lipid mediators by several researchers (Serhan et al., 2008). ...
Article
Full-text available
The purpose of this study is to see how adding the amino acid lysine to commercial feed affects the amount of EPA and DHA in catfish (Pangasius sp.) flesh. This study is an experimental study with a totally randomized design that includes four treatments and five replications. P0 (100% commercial feed + 1.2 percent amino acid lysine), P2 (100% commercial feed + 2.2 percent amino acid lysine), and P3 (100% commercial feed + 3.2 percent amino acid lysine) were the treatments. The parameters observed were EPA and DHA in catfish meat. Data analysis used ANOVA and continued with the DUNCAN test (p 0.05). The results showed that the addition of the amino acid lysine to commercial feed for 30 days of maintenance was able to increase the EPA and DHA content in catfish meat. The highest EPA content was obtained by treatment P1 (1.2% amino acid lysine), which was 0.597%, while the highest DHA content was obtained by treatment P2 (2.2% amino acid lysine), which was 0.747%. Our findings demonstrate that adding the amino acid lysine to the diet can result in nutrient-rich catfish flesh. However, studies on the influence of lysine amino acid on the growth rate, survival rate, and cholesterol ratio in catfish flesh are predicted to enhance the productivity of this very nutritious fish.
... Although DHA can be produced from α-linolenic acid, the reaction rate is low, which thus necessitates its intake from diet (7). It accumulates in retinal tissue and gray matter in general and plays a key role in early visual and neural development (162). Besides, it is conducive to the development of the retinal, neuronal and immune systems at embryonic and post-natal stages (163,164) and is effective to prevent cardiovascular disease, maintain brain and learning functions and protect inflammation response systems in adulthood (165). ...
Article
Full-text available
Oleaginous fungi (including fungus-like protists) are attractive in lipid production due to their short growth cycle, large biomass and high yield of lipids. Some typical oleaginous fungi including Galactomyces geotrichum, Thraustochytrids, Mortierella isabellina, and Mucor circinelloides, have been well studied for the ability to accumulate fatty acids with commercial application. Here, we review recent progress toward fermentation, extraction, of fungal fatty acids. To reduce cost of the fatty acids, fatty acid productions from raw materials were also summarized. Then, the synthesis mechanism of fatty acids was introduced. We also review recent studies of the metabolic engineering strategies have been developed as efficient tools in oleaginous fungi to overcome the biochemical limit and to improve production efficiency of the special fatty acids. It also can be predictable that metabolic engineering can further enhance biosynthesis of fatty acids and change the storage mode of fatty acids.
... DHA acts as an anti-inflammatory agent and constitutes a major structural component of the cell membrane (Kiecolt-Glaser et al., 2012). It usually accumulates in the brain grey matter and retinal tissues, making it important for early visual and neurological development (Lazzarin et al., 2009). Replacing SFAs with omega-3 and omega-6 fatty acids in the diet reduce the risk of cardiovascular diseases and prevent Alzheimer's, bipolar disorder, and schizophrenia (Conquer et al., 2000). ...
Article
Full-text available
The commercial production of docosahexaenoic acid (DHA) from oleaginous microorganisms is getting more attention due to several advantages over fish oils. The processing cost became a major bottleneck for commercialization of DHA from microorganisms. The most of cost shares in the feedstock to cultivate the microorganisms and downstream processing. The cost of feedstock can be compensated with the utilization of substrate from waste stream whereas production of value-added chemicals boosts the economic viability of nutraceutical production. In the present study, the docosahexaenoic acid (DHA)-producing marine protist Aurantiochytrium sp. T66 was cultivated on post-consumption food waste hydrolysate for the mining of squalene. After 120 h of cultivation, cell dry weight was 14.7 g/L, of which 6.34 g/L (43.13%; w/w) were lipids. DHA accounted for 2.15 g/L (34.05%) of total extracted lipids or 0.15 g/gCDW. Maximum squalene concentration and yield were 1.05 g/L and 69.31 mg/gCDW, respectively. Hence, utilization of food waste represents an excellent low-cost strategy for cultivating marine oleaginous thraustochytrids and produce squalene as a byproduct of DHA.
... EPA and DHA can be supplemented by eating fatty sh such as albacore tuna, salmon, mackerel, sardines, and herring (5). ω-3 Fatty acids are incorporated into numerous parts of the body (6). For example, DHA is a key component of all cell membranes (7), and EPA and DHA are precursors of metabolites that act as lipid mediators, which are assumed to be e ective in preventing or treating several diseases (8). ...
Article
Multiple studies have suggested that ω-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between ω-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018. We included meta-analyses of observational studies that examined associations between intake of fish or ω-3 fatty acid and cancer risk (gastrointestinal, liver, breast, gynecologic, prostate, brain, lung, and skin) and determined the level of evidence of associations. In addition, we appraised the quality of the evidence of significant meta-analyses by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We initially screened 598 articles, and 15 articles, including 57 meta-analyses, were eligible. Among 57 meta-analyses, 15 reported statistically significant results. We found that 12 meta-analyses showed weak evidence of an association between ω-3 fatty acid intake and risk of the following types of cancer: liver cancer (n = 4 of 6), breast cancer (n = 3 of 14), prostate cancer (n = 3 of 11), and brain tumor (n = 2 of 2). In the other 3 meta-analyses, studies of endometrial cancer and skin cancer, there were no assessable data for determining the evidence levels. No meta-analysis showed convincing, highly suggestive, or suggestive evidence of an association. In the sensitivity analysis of meta-analyses by study design, we found weak associations between ω-3 fatty acid intake and breast cancer risk in cohort studies, but no statistically significant association in case-control studies. However, the opposite results were found in case of brain tumor risk. Although ω-3 fatty acids have been studied in several meta-analyses with regard to a wide range of cancer outcomes, only weak associations were identified in some cancer types, with several limitations. Considering the nonsignificant or weak evidence level, clinicians and researchers should cautiously interpret reported associations between ω-3 fatty acid consumption and cancer risks. Adv Nutr 2020;00:1-16.
... EPA and DHA can be supplemented by eating fatty fish such as albacore tuna, salmon, mackerel, sardines, and herring (5). ω-3 Fatty acids are incorporated into numerous parts of the body (6). For example, DHA is a key component of all cell membranes (7), and EPA and DHA are precursors of metabolites that act as lipid mediators, which are assumed to be effective in preventing or treating several diseases (8). ...
Article
Multiple studies have suggested that ω-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between ω-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018. We included meta-analyses of observational studies that examined associations between intake of fish or ω-3 fatty acid and cancer risk (gastrointestinal, liver, breast, gynecologic, prostate, brain, lung, and skin) and determined the level of evidence of associations. In addition, we appraised the quality of the evidence of significant meta-analyses by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We initially screened 598 articles, and 15 articles, including 57 meta-analyses, were eligible. Among 57 meta-analyses, 15 reported statistically significant results. We found that 12 meta-analyses showed weak evidence of an association between ω-3 fatty acid intake and risk of the following types of cancer: liver cancer (n = 4 of 6), breast cancer (n = 3 of 14), prostate cancer (n = 3 of 11), and brain tumor (n = 2 of 2). In the other 3 meta-analyses, studies of endometrial cancer and skin cancer, there were no assessable data for determining the evidence levels. No meta-analysis showed convincing, highly suggestive, or suggestive evidence of an association. In the sensitivity analysis of meta-analyses by study design, we found weak associations between ω-3 fatty acid intake and breast cancer risk in cohort studies, but no statistically significant association in case-control studies. However, the opposite results were found in case of brain tumor risk. Although ω-3 fatty acids have been studied in several meta-analyses with regard to a wide range of cancer outcomes, only weak associations were identified in some cancer types, with several limitations. Considering the nonsignificant or weak evidence level, clinicians and researchers should cautiously interpret reported associations between ω-3 fatty acid consumption and cancer risks.
... EPA and DHA are ω-3 long-chain PUFA dietary fats with several health benefits. EPA and DHA are assimilated in several body locations comprising cell membranes (Lazzarin et al., 2009) and take part in antiinflammatory procedures and in the viscosity of cell membranes (Conquer, Tierney, Zecevic, Bettger, & Fisher, 2000;Smith et al., 2011). They are as well the forerunners of many metabolites, which are strong lipid mediators, treated by many researchers as valuable components in the anticipation or management of numerous illnesses (Serhan, Chiang, & Van Dyke, 2008). ...
Chapter
Fish is regarded as a healthy animal-derived food owing to its remarkable content in macro and micronutrients, which results in a large consumption by humans. Consequently, fishery-related industries generate huge amounts of byproducts that are frequently used to manufacture low-value products or are even discarded. Nevertheless, these marine derivatives present interesting high-value functional features that can be exploited, due to their importance, in the food or nutraceutical industries. In order to obtain these compounds of interest, such as bioactive lipids, it is important to select suitable extraction methods. It is of current concern the use of alternative green cutting edge technologies such as ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE) or supercritical fluid extraction (SFE), which possess some advantages over conventional extractions methods, improving the quality of the extracts and reducing the loss of functional properties of the bioactive compounds obtained. The potential use, and advantages and drawbacks of UAE, MAE, and SFE for the obtainment of lipids from fish derivatives were pinpointed and discussed, in addition to the beneficial effect to the bioactive lipids in human health.
... The consumption of fish and seafood has a positive influence on health-a fact that is supported by numerous studies. The main advantage of fish is the content of omega-3 fatty acids, Vitamin D and minerals, including iodine [30]. Some of the most important elements of the diet are fatty sea fish, i.e., salmon, herring, mackerel-the ones that are the richest in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) fatty acids. ...
Article
Full-text available
Introduction: The diet of Poles became similar to the western style of nutrition. It is rich in saturated fats, it contains significant quantities of salt, and has very low fruit and vegetable content. On the other hand, introducing an incorrectly planned diet that eliminates animal products may be associated with the risk of deficiencies of certain vitamins and minerals. Taking into account the regular diet of Poles, a properly balanced vegetarian menu may be a better and safer choice for the proper functioning of the organism. Aim: The analysis of the content of individual types of vegetarian diets and a comparison with the menus of the regular diet of the Polish population. Materials and methods: 70 menus were subjected to a quantitative analysis, 10 menus for each 7 type of diet eliminating products of animal origin and regular diets without elimination. The caloricity of the designed diets was ±2000 kcal. The quantitative evaluation of the menus was performed using the Dieta 6d dietary program. Statistical significance was established at p ≤ 0.05. Results: It was observed that the regular diet of Poles (RD) featured the highest content of total fats, as well as saturated acids and cholesterol. The VEGAN diet was characterized by the lowest total protein content and the lack of wholesome protein and cholesterol. RD was characterized by the lowest average content of dietary fiber. The highest content of saccharose was observed in RD. Sodium content in RD significantly exceeded the recommended daily norm. RD featured insufficient content of the following minerals and vitamins: potassium, calcium, magnesium, iodine, Vitamin E, Vitamin C, folates, and Vitamin D. The norm for calcium has not been fulfilled also in milk-free and vegan diets. All of the analyzed diets lacked proper amounts of iodine and Vitamin D. The highest content of polyunsaturated fatty acids was observed in the VEGAN diet. The periodic elimination of meat and fatty dairy products should be included in the treatment of the metabolic syndrome, hypertensions, hyperlipidemia, obesity, and type 2 diabetes. Conclusions: The regular diet of Poles turned out to be more dangerous for health in terms of deficiencies than properly balanced diets eliminating products of animal origin.
... The consumption of fish and seafood has a positive influence on health-a fact that is supported by numerous studies. The main advantage of fish is the content of omega-3 fatty acids, Vitamin D and minerals, including iodine [30]. Some of the most important elements of the diet are fatty sea fish, i.e., salmon, herring, mackerel-the ones that are the richest in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) fatty acids. ...
Article
Full-text available
Abstract Introduction: In recent decades, the number of gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) cases, associated with coexisting metabolic disorders, has been continuously increasing. Patients with progressing neoplastic disease are at a risk of malnutrition. To improve the quality of life of neuroendocrine neoplasms (NEN) patients, the therapeutic approach should be supported by a well-balanced diet. The aim of the study was to analyze the nutritional errors and deficits in a group of GEP-NET patients. Materials and methods: The study group included 26 GEP-NET patients; 13 men and 13 women. The mean age of women was 68.77 ± 8.0, and the mean age of men was 64.69 ± 8.1. Three interviews on consumption in the last 24 h were performed, in order to evaluate the quality and quantity of nutrition. The data was incorporated into a dietetics software, which allows one to calculate the number of over 58 micronutrients and macronutrients with the participation of 52 menus. Subsequently, the mean values were compared with the current nutritional standards. Results: An energy deficit was observed in the group of women—76.9%, and men—100%, as well as high fat consumption in 23.1% in both groups. The proportions of SFA/MUFA/PUFA were very negative, whereas the consumption of saccharose was too high. Vitamin D deficiency was observed in 100% of men and women. Moreover, both men and women experienced the deficiency of vitamin E, folates and niacin. The consumption of sodium and phosphorus was twice as high as recommended, and an insufficient supply of calcium was observed in 80% of women and 90% of men. The insufficient consumption of magnesium, iodine and potassium in a significant part of the studied group was observed. All participants consumed too much cholesterol and insufficient amounts of fiber. The healthy diet indicator (HDI) and diet quality index (DQI) scores were 3.1 ± 1.8 (HDI) and 3.7 ± 1.6 (DQI) for women, and 7.2 ± 2.6 (HDI) and 8.5 ± 2.4 (DQI) for men. Conclusions: When analyzing the nutrition of GEP-NET patients, we highlight that they do not have a proper diet, despite the fact that they changed the way they eat. Dietetics support and the development of official nutritional standards seem to be a necessary element in the therapy of GEP-NET patients. Keywords: neuroendocrine neoplasms; gastroenteropancreatic neuroendocrine neoplasms; nutrition; methods of nutrition; nutritional status
... In the cell level, DHA synthesizes cell membranes and other tissues (Lazzarin et al. 2009;Kiecolt-Glaser et al. 2012). ...
Chapter
Marine microorganisms are microscopic organisms that live in oceans. In the oceans, more than 98% of the biomass is contributed by marine microorganisms. They play a role in earth for the mass and energy balance by mass and energy flow worldwide. Almost all of the marine products are made of marine microorganisms. In marine ecosystems, biomass keeps the dynamic balance between the producers and the consumers. The deepest part of the ocean is beneath 10,984 m. The pressure is 1100-fold of the standard air pressure. Because of the different metabolic pathways, marine microorganisms are sources of novel biomolecules, such as bio-surfactants. In the battle to degrade the pollutants, they are key players. Currently, more than 30,000 chemicals have been discovered in the marine. Many of them are useful substances in industries. For example, they have the abilities to degrade pollutants like antibacterial, antifungal, antivirus, and antitumor properties, and have functions in foods and enzymes. Marine microorganisms are used as pollutant degraders in other added value products.
... Additionally, the application of LMWH can improve uterine artery blood flow and help obtain good pregnancy outcomes in uRPL patients with increased URA-RI (45). Reportedly, alternative therapeutic approaches comprising nitric oxide, sildenafil, omega 3, and vitamin E can also increase uterine artery blood flow in pregnancy complications (36,(149)(150)(151). ...
Article
Full-text available
The invasion of trophoblasts into the uterine decidua and decidual vessels is critical for the formation of placenta. The defects of placentation are related to the etiologies of preeclampsia (PE), fetal growth restriction (FGR), and small-for-gestational age (SGA) neonates. It is possible to predict significant vascular events during pregnancy through uterine artery Doppler (UAD). From the implantation stage to the end of pregnancy, detecting changes in uterine and placental blood vessels can provide a favorable diagnostic instrument for pregnancy complications. This review aims to collect literature about the roles of UAD in pregnancy complications. We consider all relevant articles in English from January 1, 1983 to October 30, 2021. Predicting pregnancy complications in advance allows practitioners to carry out timely interventions to avoid or lessen the harm to mothers and neonates. Administering low-dose aspirin daily before 16 weeks of pregnancy can significantly reduce the incidence of pregnancy complications. From early pregnancy to late pregnancy, UAD can combine with other maternal factors, biochemical indicators, and fetal measurement data to identify high-risk population. The identification of high-risk groups can also lessen maternal mortality. Besides, through moderate risk stratification, stringent monitoring for high-risk pregnant women can be implemented, decreasing the incidence of adversities.
... Omega-3 is a long-chain of Polyunsaturated fatty acids (PUFA), including Eicosapentaenoic acid (EPA) and Doxohexaenoic acid (DHA), are dietary fats had an important health benefits (1). They are incorporated in many parts of the body including cell membranes (2). It is play a role in anti-inflammatory and in viscosity of cell membranes (3,4). ...
Article
Full-text available
The current study aimed to investigate the effects of Omega 3 and fish oil on some physiological and antioxidant parameters in Male rabbits. Twelve male rabbits adult and divided into two groups, group 1 (G1) received 0.2 ml/kg B.W Omega 3 orally for 4 weeks and group 2 (G2) revived 0.2 ml/kg B.W fish oil orally for 4 weeks. Blood collected from G1 in pretreated period and served as control for G1 and G2 also blood collected in zero day of the experiment and used as control for G2 (pretreated period). The blood collected without anticoagulant and serum separated for biochemical and antioxidant parameters measurement. The results showed a significant (P ≤ 0.05) decrease in Superoxide dismutase (SOD), Glutathione peroxidase (GPX) and Malondialdehyde (MDA) in Omega3 treated group as compared with control (pretreated period). The current results clarified there was no-significant (P ≤ 0.05) difference in Catalase (CAT) and significant (P ≤ 0.05) increase in Glutathione (GSH) in Omega 3 treated group as compared with control group. The vitamin C decreased significantly (P ≤ 0.05) in Omega 3 group as compared with control with no-significant (P ≤ 0.05) increase or decrease in vitamin E concentration. There was no-significant (P ≤ 0.05) increase or decrease in total protein concentration, Albumin and globulin in Omega 3 treated group as compared with control. The rabbits received fish oil orally daily for four weeks clarified a significant (P ≤ 0.05) decrease in SOD, GPX, MDA, and Vitamin C as compared with control. While there was significant (P ≤ 0.05) increase in GSH as compared with control and there was no-significant (P ≤ 0.05) change in CAT activity and Vitamin E concentration as compared with control. Also the fish oil treated group revealed that there was no-significant (P ≤ 0.05) change in total protein concentration, Albumin and globulin as compared with control.
... Omega-3 is a fatty acid that may have potential for preventing miscarriage. In a prospective study, omega-3 combined with aspirin improved the uterine artery blood flow velocity in women with recurrent miscarriage [222]. However, the literature on the relationship between human serum omega-3 concentration and reproduction is limited specifically to infertile people, and whether it can prevent miscarriage is still controversial [223,224]. ...
Article
Full-text available
Threatened miscarriage is one of the most common complications causing pregnancy loss, and it affects approximately 20% of confirmed pregnancies. More and more women are seeking treatment with complementary and alternative medicine (CAM) for this common complication, and it has been reported that women have had successful pregnancies after threatened miscarriage when being treated with CAM, which mainly includes Chinese herbal medicines, acupuncture, and nutritional supplements as well as psychological interventions and other approaches. However, many experts are concerned about the safety and adverse events of certain CAM approaches in women with threatened miscarriage. Therefore, this review focuses on the status of CAM for threatened miscarriage and presents the potential therapeutic efficacy and safety of CAM based on some clinical and experimental studies. We thus hope to provide some instructive suggestions for the application of CAM for treating threatened miscarriage in the future.
Article
Objective: To evaluate subendometrial blood flow in women with a history of recurrent unexplained abortion compared with women who had at least one live child and no history of spontaneous abortions. Setting: Kasr El Aini Hospital. Design: Cross-sectional study. Participants and methods: Fifty women with recurrent pregnancy loss were compared with 50 women with no history of abortion and at least one child born at term. Transvaginal 3D power Doppler ultrasonography was performed in all patients in the second phase of a nonpregnant unstimulated cycle to detect the uterine artery pulsatility index and the subendometrial area to detect subendometrial blood flow presented by the following indices: vascularization index, flow index, and vascular flow index. Results: The vascular flow index was higher in the control group (1.2048±1.11649) than in the case group (0.71254±0.6522), which was statistically significant (P=0.048). Endometrial thickness was higher in the case group (10.139±0.9539) than in the control group (9.671±0.8609), which was statistically significant (P=0.006). Conclusion: Subendometrial blood flow is altered in women with recurrent miscarriage cases and patients with unexplained recurrent pregnancy loss may have abnormalities in the uterine and endometrial blood flow.
Article
Background and purpose: Abortion is considered recurrent when it spontaneously occurs at least three times. Recent studies suggest a correlation between uterine artery resistance and recurrent miscarriage (RM). There are few studies on the ovarian arteries. Therefore, this study evaluated the resistance of uterine and ovarian arteries in unexplained recurrent miscarriage and normal fertile women. Material and methods: The participants included women with history of unexplained recurrent miscarriage (study group, no. = 57). Also, 57 healthy fertile women were selected as a control group. Transvaginal power Doppler ultrasonography was performed for all patients in the midluteal phase of the nonpregnant subjects to detect uterine and ovarian arteries pulsatility index (PI) and resistance index (RI). The indices were then compared between the two groups. Results: The women with recurrent pregnancy loss had a significantly higher uterine artery PI and RI compared with those of the control group (2.4 ± 0.31 vs. 1.9 ± 0.28 for PI and 0.84 ± 0.31 vs. 0.63 ± 0.29 for RI), but the two groups did not have any significant difference in ovarian artery PI and RI (0.81 ± 0.19 vs. 0.7 ± 0.18 for PI and 0.52 ± 0.11 vs. 0.4 ± 0.13 for RI). Conclusion: Uterine arterial resistance is associated with RM. This study also showed the efficacy of Pulsed Doppler ultrasonography in identifying women with unexplained RM who have impaired uterine circulation. Hence, screening should be carried out to detect individuals at risk, thereby decrease the rate of RM. However, additional studies are recommended to verify and further clarify these results.
Conference Paper
Insulin resistance (IR), characterized by up-regulation of systemic pro-inflammatory biomarkers, is on the rise in human and the domestic horse and the condition shares similar morbidities within the two species. Impacts on reproduction include early pregnancy loss in humans and lengthened inter-ovulatory period in horses. Ingestion of the polyunsaturated fatty acids omega-3 have been linked to improved health outcomes in humans and may be beneficial to early embryonic development. In this study, we compared the uterine fluid (histotroph) proteome of insulin sensitive (IS) vs. insulin resistant (IR) mares and examined the impact of algal-derived n-3 LCPUFA (primarily DHA) supplementation (DHA; 0.06 g/kg BWT daily) on histotroph composition during early pregnancy (12.5 d). Mares (n = 8; n = 2 per metabolic and dietary status) were monitored via ultrasonography and inseminated using fresh sperm (250 x 106 progressively motile). Pregnancy was detected via ultrasonography and uterine fluid along with the embryo was collected by infusion of Lactated Ringers solution followed by gravity flow recovery at 12.5 d post-ovulation. Uterine fluid was pooled for metabolic and dietary categories and concentrated using a 3 kDa cut-off centrifugation filter. Total protein (100 µg) was analyzed using mass spectrometry (LC-MS/MS; iTRAQ) and proteins identified by comparing mass spectra against the Equus caballus non-redundant RefSeq protein (20130923 build) using Proteome Discoverer 1.4. The criteria for declaring differential expression of a protein between metabolic and dietary groups was set at ± 1.5-fold change with statistical significance (P < 0.05). Differentially expressed proteins were analyzed using PANTHER® for biological function and overrepresentation. Proteome analysis identified 606 proteins. Sixty proteins met criteria in Control (C), IR mares when compared to C, IS counterparts (47 up-regulated and 13 down-regulated) and PANTHER® identified proteolysis function as most overrepresented. Comparison of uterine fluid from DHA supplemented, IS vs. C, IS mares identified 57 differentially expressed proteins (28 up-regulated and 29 down-regulated) and proteolysis was found to be most overrepresented. Comparison of DHA supplemented, IR mares to C, IR counterparts, identified 56 proteins differentially expressed proteins (15 up-regulated and 41 down-regulated) and complement activation was the most overrepresented function. Furthermore, most differentially expressed proteins were involved in regulation of metabolism. Six proteins including Ig mu chain C membrane bound form, keratin, type II cytoskeletal 1, protein S100-A11, afamin, serotransferrin and serum amyloid A (SAA) met differential expression criteria in all of the above comparisons. Expression of afamin and SAA were both up-regulated in C, IR mares when compared to C, IS, (3 and 3.3-fold, respectively) but down-regulated in DHA, IR when compared to C, IR. Differential expression of SAA was confirmed via western blot analysis of uterine fluid and serum as well as immunohistochemistry on endometrial glandular epithelium in early pregnant IR mares. SAA is the major acute phase (pro-inflammatory) protein in horses and is associated with non-specific inflammation. These findings provide novel information on the impact of insulin resistance on the secreted uterine proteome in horses. We also provide evidence that dietary omega-3 may exert anti-inflammatory effects on IR uterine secretory products.
Article
Background: The aim of the study is to evaluate the effects of supplementation with Arginine (L-Arg) 3g, (together with Magnesium (Mg) 350 mg and Salicilate (Sal) 100 mg) on maternal blood pressure (BP), uterine artery doppler PI and neonatal outcomes in women with high-risk pregnancy for chronic hypertension (CH) and other previous placenta vascular disorders (PVD) already treated with low dose of aspirin (LDA), as recommended by guidelines. Methods: We enrolled women affected by CH and other previous PVD referred to the High-Risk Clinic of the Mother-Infant Department of the University of Modena and Reggio Emilia from September 2017 to June 2019. The study design was a controlled, randomized trial of oral supplementation of L-Arg 3g (together with Mg 350 mg and Sal extract 100 mg) + LDA 100 mg/die versus only LDA 100 mg/die. Inclusion criteria were: singleton pregnancy; diagnosis of chronic hypertension, previous preeclampsia < 34 weeks, previous intrauterine growth restriction (IUGR) < 10° centile or previous stillbirth (SB) related to placenta vascular disorders; gestational age < 14 weeks. Each woman was enrolled between 12-14 weeks gestation and underwent 24-h ambulatory BP monitoring with an automatic device (SpaceLab 92710, Critikon, WA), repeated at 18-20th and 24-26th weeks. Moreover Uterine artery Doppler ultrasound evaluation including PI were performed at 18-20 weeks gestation and repeated at 24-26th weeks. Pregnancy outcomes data were collected in a password protected database. Results: Seventy-nine women agreed to participate in the study. No significant differences between the demographic characteristics in the two groups at enrollment (Group LDA + L-Arg: 30 patients versus Group LDA: 49 patient) were found. In the LDA-L-Arg group there isn't the significant increase in both systolic (127.22 ± 12.02 and 132.75 ± 7.51 mmHg, p=0.002) and diastolic (75.85 ± 8.53 and 83.63 ± 6.05 mmHg, p=0.0000) BP values at 24-26 weeks reveled in the LDA group. The value of the Uterine Artery Doppler median PI > 95° centile at 24-26 weeks show a significant reduction in the LDA+L-Arg group respect the LDA group (7 women, 23.3% vs 21 women, 42.9%; p=0.04). A significantly lower percentage of women received new antihypertensive drugs in the LDA+ L-Arg group than the LDA group (6.7% vs 24.5%) (p= 0.02). There was neither statistically significant difference in perinatal outcomes between 2 groups, except for trend of significance. Conclusions: Although we found only trends of improvements of perinatal outcomes in LDA+LArg group, considering the promising results on BP values, uterine artery PI and the low need to start a new antihypertensive treatment, thus the resulting impact in reducing pregnancy medicalization, number of maternal-fetal well-being monitoring visits and the need of induction of labour, we believe that further studies should be performed to enlarge our observation and clarify the role of L-Arg 3g supplementation as a protective integration in high-risk pregnancies already in prophylaxis with LDA.
Chapter
We recently developed an animal model of hyperglycaemia during pregnancy to investigate the molecular mechanisms underlying cardiac abnormalities observed in infants of diabetic mothers (IDMs). Furthermore, we explored the diet that should be consumed to improve the abnormalities by a molecular nutritional study and investigated the potential molecular pathway for this effect in the animal model. Assessment of newborn rat hearts revealed that altered insulin signalling-induced insulin resistance by inhibiting the Akt/mammalian target of rapamycin (mTOR) pathway, which was improved in the offspring of rats that were fed a fish oil-rich diet. Here, we describe the significance of consuming fish oil during pregnancy in the first section of this chapter. The second section deal with the potential molecular pathways involved in EPA-mediated regulation of cardiac function. Studies have demonstrated that intrauterine foetal exposure to hyperglycaemia during pregnancy was associated with cardiovascular complications, such as cardiomyocyte hypertrophy, in infants of diabetic mothers (IDMs). We recently developed an animal model of hyperglycaemia during pregnancy to investigate the molecular mechanisms underlying cardiac abnormalities observed in IDMs. Furthermore, we explored the diet that should be consumed to improve the abnormalities by a molecular nutritional study and investigated the potential molecular pathway for this effect in the animal model. Assessment of newborn rat hearts revealed that altered insulin signalling-induced insulin resistance by inhibiting the Akt/mammalian target of rapamycin (mTOR) pathway, which was improved in the offspring of rats that were fed a fish oil-rich diet. Nevertheless, specific ingredients of fish oil that are responsible for improving abnormal insulin signalling remain unclear. Fish oil is present in many types of seafood, particularly fatty fish, and contains high docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels, both of which are omega-3 polyunsaturated fatty acids (PUFAs). Consuming fish oil lowers plasma triglyceride levels, resting heart rate and blood pressure and reduces inflammation and improves vascular function. Consuming EPA is also associated with improvements in patients with cardiovascular diseases. Here, we describe the significance of consuming fish oil during pregnancy in the first section of this chapter. The second section examines the potential molecular pathways involved in EPA-mediated regulation of cardiac function. EPA influences a myriad of molecular signalling pathways by altering the functions of key enzymes via membrane and nuclear receptors and transcription factors and through changes in the eicosanoid profiles. Therefore, EPA may have beneficial effects on foetal heart, providing protection from a hyperglycaemic intrauterine environment in pregnant diabetic mothers.
Article
Objective: To evaluate differences in Doppler parameters and pregnancy outcomes, if any, and to determine the predictive accuracy of such indices, as well as the effects of low-dose aspirin (LDA) in unexplained recurrent pregnancy loss (URPL). Methods: An observational study was conducted at Ren Ji Hospital, Shanghai, China, from May 2015 to December 2016. The endometrial thickness, and the pulsatility index (PI), resistive index (RI), and systolic-to-diastolic ratio (S/D) values of endometrial and uterine artery blood flow were collected. Receiver operating characteristic (ROC) curve analysis was used to analyze data from URPL patients (three or more first-trimester spontaneous abortions with unknown etiology) and patients with normal fertility. A second ultrasonography examination was performed in URPL patients who had received daily LDA for 2 months. Results: There were 190 URPL patients and 35 control patients. Endometrial thickness was significantly thinner in URPL patients than control patients (P=0.005). The PI, RI, and S/D values for endometrial blood flow and the mean PI, RI, and S/D values for uterine arteries were significantly higher in URPL patients (P<0.001). The predictive accuracy of the indices mentioned above were 0.660, 0.802, 0.852, 0.837, 0.784, 0.929, and 0.929, respectively. Following LDA supplementation, URPL patients showed a significant reduction in resistance to endometrial and uterine artery blood flow (P<0.001). Conclusion: URPL patients had impaired uterine perfusion. Doppler parameters are valuable in predicting women at high risk of URPL. LDA could be effective in improving endometrial receptivity.
Article
Purpose: To assess the sub endometrial and uterine artery blood flow and pattern of waveform of uterine artery in cases of recurrent pregnancy loss, compared to normal controls. Subjects and methods: Fifty women with a history of two or more successive pregnancy losses were investigated by Doppler transvaginal ultrasound to assess the sub endometrial blood flow resistance index, type of Doppler waveform of uterine artery, and uterine artery pulsatility index in the midluteal phase. Fifty normal women acted as controls. Results: Sub endometrial blood flow resistance index (RI) and uterine artery pulsatility index (PI) were higher in cases than controls. The majority of cases of recurrent pregnancy loss had a waveform pattern of A, or loss of diastolic flow, while the controls were mainly C wave. Conclusion: Some sort of endometrial and sub endometrial ischemia can be suggested in cases of recurrent pregnancy loss, waveform pattern of uterine artery changes may be used to monitor changes in vascularity of endometrium if vascular enhancers are given in such cases.
Article
Full-text available
Background: There is a substantial body of research evaluating ways to prevent and manage miscarriage, but studies do not report on the same outcomes. Objective: To systematically review outcomes reported in existing miscarriage trials. Search strategy: MEDLINE, Embase, CINAHL and Cochrane were searched from inception until January 2017. Selection criteria: Randomised controlled trials (RCTs) reporting prevention or management of miscarriage. Miscarriage was defined as a pregnancy loss in the first trimester. Data collection and analysis: Data about the study characteristics, primary and secondary outcomes were extracted. Main results: We retrieved 1,553 titles and abstracts, from which 208 RCTs were included. For prevention of miscarriage the most commonly reported primary outcome was live birth and the top four reported outcomes were pregnancy loss/stillbirth (n=112), gestation of birth (n=68), birth dimensions (n=65) and live birth (n=49). For these four outcomes, 58 specific measures were used for evaluation. For management of miscarriage the most commonly reported primary outcome was efficacy of treatment. The top four reported outcomes were bleeding (n=186), efficacy of miscarriage treatment (n=105), infection (n=97) and quality of life (n=90). For these outcomes, 130 specific measures were used for evaluation. Conclusions: Our review found considerable variation in the reporting of primary and secondary outcomes along with the measures used to assess them. There is a need for standardised patient-centred clinical outcomes through the development of a core outcome set; the work from this systematic review will form the foundation of the core outcome set for miscarriage. This article is protected by copyright. All rights reserved.
Article
Background: Higher intakes of foods containing omega-3 long-chain polyunsaturated fatty acids (LCPUFA), such as fish, during pregnancy have been associated with longer gestations and improved perinatal outcomes. This is an update of a review that was first published in 2006. Objectives: To assess the effects of omega-3 LCPUFA, as supplements or as dietary additions, during pregnancy on maternal, perinatal, and neonatal outcomes and longer-term outcomes for mother and child. Search methods: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (16 August 2018), and reference lists of retrieved studies. Selection criteria: Randomised controlled trials (RCTs) comparing omega-3 fatty acids (as supplements or as foods, stand-alone interventions, or with a co-intervention) during pregnancy with placebo or no omega-3, and studies or study arms directly comparing omega-3 LCPUFA doses or types. Trials published in abstract form were eligible for inclusion. Data collection and analysis: Two review authors independently assessed study eligibility, extracted data, assessed risk of bias in trials and assessed quality of evidence for prespecified birth/infant, maternal, child/adult and health service outcomes using the GRADE approach. Main results: In this update, we included 70 RCTs (involving 19,927 women at low, mixed or high risk of poor pregnancy outcomes) which compared omega-3 LCPUFA interventions (supplements and food) compared with placebo or no omega-3. Overall study-level risk of bias was mixed, with selection and performance bias mostly at low risk, but there was high risk of attrition bias in some trials. Most trials were conducted in upper-middle or high-income countries; and nearly half the trials included women at increased/high risk for factors which might increase the risk of adverse maternal and birth outcomes.Preterm birth < 37 weeks (13.4% versus 11.9%; risk ratio (RR) 0.89, 95% confidence interval (CI) 0.81 to 0.97; 26 RCTs, 10,304 participants; high-quality evidence) and early preterm birth < 34 weeks (4.6% versus 2.7%; RR 0.58, 95% CI 0.44 to 0.77; 9 RCTs, 5204 participants; high-quality evidence) were both lower in women who received omega-3 LCPUFA compared with no omega-3. Prolonged gestation > 42 weeks was probably increased from 1.6% to 2.6% in women who received omega-3 LCPUFA compared with no omega-3 (RR 1.61 95% CI 1.11 to 2.33; 5141 participants; 6 RCTs; moderate-quality evidence).For infants, there was a possibly reduced risk of perinatal death (RR 0.75, 95% CI 0.54 to 1.03; 10 RCTs, 7416 participants; moderate-quality evidence: 62/3715 versus 83/3701 infants) and possibly fewer neonatal care admissions (RR 0.92, 95% CI 0.83 to 1.03; 9 RCTs, 6920 participants; moderate-quality evidence - 483/3475 infants versus 519/3445 infants). There was a reduced risk of low birthweight (LBW) babies (15.6% versus 14%; RR 0.90, 95% CI 0.82 to 0.99; 15 trials, 8449 participants; high-quality evidence); but a possible small increase in large-for-gestational age (LGA) babies (RR 1.15, 95% CI 0.97 to 1.36; 6 RCTs, 3722 participants; moderate-quality evidence, for omega-3 LCPUFA compared with no omega-3. Little or no difference in small-for-gestational age or intrauterine growth restriction (RR 1.01, 95% CI 0.90 to 1.13; 8 RCTs, 6907 participants; moderate-quality evidence) was seen.For the maternal outcomes, there is insufficient evidence to determine the effects of omega-3 on induction post-term (average RR 0.82, 95% CI 0.22 to 2.98; 3 trials, 2900 participants; low-quality evidence), maternal serious adverse events (RR 1.04, 95% CI 0.40 to 2.72; 2 trials, 2690 participants; low-quality evidence), maternal admission to intensive care (RR 0.56, 95% CI 0.12 to 2.63; 2 trials, 2458 participants; low-quality evidence), or postnatal depression (average RR 0.99, 95% CI 0.56 to 1.77; 2 trials, 2431 participants; low-quality evidence). Mean gestational length was greater in women who received omega-3 LCPUFA (mean difference (MD) 1.67 days, 95% CI 0.95 to 2.39; 41 trials, 12,517 participants; moderate-quality evidence), and pre-eclampsia may possibly be reduced with omega-3 LCPUFA (RR 0.84, 95% CI 0.69 to 1.01; 20 trials, 8306 participants; low-quality evidence).For the child/adult outcomes, very few differences between antenatal omega-3 LCPUFA supplementation and no omega-3 were observed in cognition, IQ, vision, other neurodevelopment and growth outcomes, language and behaviour (mostly low-quality to very low-quality evidence). The effect of omega-3 LCPUFA on body mass index at 19 years (MD 0, 95% CI -0.83 to 0.83; 1 trial, 243 participants; very low-quality evidence) was uncertain. No data were reported for development of diabetes in the children of study participants. Authors' conclusions: In the overall analysis, preterm birth < 37 weeks and early preterm birth < 34 weeks were reduced in women receiving omega-3 LCPUFA compared with no omega-3. There was a possibly reduced risk of perinatal death and of neonatal care admission, a reduced risk of LBW babies; and possibly a small increased risk of LGA babies with omega-3 LCPUFA.For our GRADE quality assessments, we assessed most of the important perinatal outcomes as high-quality (e.g. preterm birth) or moderate-quality evidence (e.g. perinatal death). For the other outcome domains (maternal, child/adult and health service outcomes) GRADE ratings ranged from moderate to very low, with over half rated as low. Reasons for downgrading across the domain were mostly due to design limitations and imprecision.Omega-3 LCPUFA supplementation during pregnancy is an effective strategy for reducing the incidence of preterm birth, although it probably increases the incidence of post-term pregnancies. More studies comparing omega-3 LCPUFA and placebo (to establish causality in relation to preterm birth) are not needed at this stage. A further 23 ongoing trials are still to report on over 5000 women, so no more RCTs are needed that compare omega-3 LCPUFA against placebo or no intervention. However, further follow-up of completed trials is needed to assess longer-term outcomes for mother and child, to improve understanding of metabolic, growth and neurodevelopment pathways in particular, and to establish if, and how, outcomes vary by different types of omega-3 LCPUFA, timing and doses; or by characteristics of women.
Article
Background: Stillbirth affects at least 2.6 million families worldwide every year and has enduring consequences for parents and health services. Parents entering a subsequent pregnancy following stillbirth face a risk of stillbirth recurrence, alongside increased risks of other adverse pregnancy outcomes and psychosocial challenges. These parents may benefit from a range of interventions to optimise their short- and longer-term medical health and psychosocial well-being. Objectives: To assess the effects of different interventions or models of care prior to and during subsequent pregnancies following stillbirth on maternal, fetal, neonatal and family health outcomes, and health service utilisation. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 June 2018), along with ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (18 June 2018). Selection criteria: We included randomised controlled trials (RCTs) and quasi-randomised controlled trials (qRCTs). Trials using a cluster-randomised design were eligible for inclusion, but we found no such reports. We included trials published as abstract only, provided sufficient information was available to allow assessment of trial eligibility and risk of bias. We excluded cross-over trials. Data collection and analysis: Two review authors independently assessed trials for eligibility and undertook data extraction and 'Risk of bias' assessments. We extracted data from published reports, or sourced data directly from trialists. We checked the data for accuracy and resolved discrepancies by discussion or correspondence with trialists, or both. We conducted an assessment of the quality of the evidence using the GRADE approach. Main results: We included nine RCTs and one qRCT, and judged them to be at low to moderate risk of bias. Trials were carried out between the years 1964 and 2015 and took place predominantly in high-income countries in Europe. All trials assessed medical interventions; no trials assessed psychosocial interventions or incorporated psychosocial aspects of care. Trials evaluated the use of antiplatelet agents (low-dose aspirin (LDA) or low-molecular-weight heparin (LMWH), or both), third-party leukocyte immunisation, intravenous immunoglobulin, and progestogen. Trial participants were women who were either pregnant or attempting to conceive following a pregnancy loss, fetal death, or adverse outcome in a previous pregnancy.We extracted data for 222 women who had experienced a previous stillbirth of 20 weeks' gestation or more from the broader trial data sets, and included them in this review. Our GRADE assessments of the quality of evidence ranged from very low to low, due largely to serious imprecision in effect estimates as a result of small sample sizes, low numbers of events, and wide confidence intervals (CIs) crossing the line of no effect. Most of the analyses in this review were not sufficiently powered to detect differences in the outcomes assessed. The results presented are therefore largely uncertain.Main comparisonsLMWH versus no treatment/standard care (three RCTs, 123 women, depending on the outcome)It was uncertain whether LMWH reduced the risk of stillbirth (risk ratio (RR) 2.58, 95% CI 0.40 to 16.62; 3 trials; 122 participants; low-quality evidence), adverse perinatal outcome (RR 0.81, 95% CI 0.20 to 3.32; 2 trials; 77 participants; low-quality evidence), adverse maternal psychological effects (RR 1.00, 95% CI 0.07 to 14.90; 1 trial; 40 participants; very low-quality evidence), perinatal mortality (RR 2.58, 95% CI 0.40 to 16.62; 3 trials; 122 participants; low-quality evidence), or any preterm birth (< 37 weeks) (RR 1.01, 0.58 to 1.74; 3 trials; 114 participants; low-quality evidence). No neonatal deaths were reported in the trials assessed and no data were available for maternal-infant attachment. There was no clear evidence of a difference between the groups among the remaining secondary outcomes.LDA versus placebo (one RCT, 24 women)It was uncertain whether LDA reduced the risk of stillbirth (RR 0.85, 95% CI 0.06 to 12.01), neonatal death (RR 0.29, 95% CI 0.01 to 6.38), adverse perinatal outcome (RR 0.28, 95% CI 0.03 to 2.34), perinatal mortality, or any preterm birth (< 37 weeks) (both of the latter RR 0.42, 95% CI 0.04 to 4.06; all very low-quality evidence). No data were available for adverse maternal psychological effects or maternal-infant attachment. LDA appeared to be associated with an increase in birthweight (mean difference (MD) 790.00 g, 95% CI 295.03 to 1284.97 g) when compared to placebo, but this result was very unstable due to the extremely small sample size. Whether LDA has any effect on the remaining secondary outcomes was also uncertain.Other comparisonsLDA appeared to be associated with an increase in birthweight when compared to LDA + LMWH (MD -650.00 g, 95% CI -1210.33 to -89.67 g; 1 trial; 29 infants), as did third-party leukocyte immunisation when compared to placebo (MD 1195.00 g, 95% CI 273.35 to 2116.65 g; 1 trial, 4 infants), but these results were again very unstable due to extremely small sample sizes. The effects of the interventions on the remaining outcomes were also uncertain. Authors' conclusions: There is insufficient evidence in this review to inform clinical practice about the effectiveness of interventions to improve care prior to and during subsequent pregnancies following a stillbirth. There is a clear and urgent need for well-designed trials addressing this research question. The evaluation of medical interventions such as LDA, in the specific context of stillbirth prevention (and recurrent stillbirth prevention), is warranted. However, appropriate methodologies to evaluate such therapies need to be determined, particularly where clinical equipoise may be lacking. Careful trial design and multicentre collaboration is necessary to carry out trials that would be sufficiently large to detect differences in statistically rare outcomes such as stillbirth and neonatal death. The evaluation of psychosocial interventions addressing maternal-fetal attachment and parental anxiety and depression is also an urgent priority. In a randomised-trial context, such trials may allocate parents to different forms of support, to determine which have the greatest benefit with the least financial cost. Importantly, consistency in nomenclature and in data collection across all future trials (randomised and non-randomised) may be facilitated by a core outcomes data set for stillbirth research. All future trials should assess short- and longer-term psychosocial outcomes for parents and families, alongside economic costs of interventions.
Chapter
Certain omega‐3 fatty acids, such as α‐linolenic acid (ALA), and omega‐6 fatty acids, such as linoleic acid (LA), cannot be synthesized in the human body and are recognized as essential fatty acids. While some long‐chain polyunsaturated fatty acids (LC‐PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be synthesized from the parent omega‐3 fatty acids (ALA), this is done at a very low conversion rate, hence it must be taken through diet to fulfill the daily intake requirement. Both EPA and DHA have several vital activities in the human body, such as anti‐inflammatory effects and being the structural component of the cell membrane. The fatty acids DHA, arachidonic acid (AA), and LA accumulate most usually in tissues, whereas DHA mostly accumulates in retina and brain gray matters and it is important for proper visual and neurological development during gestation period and postnatal period. Replacement of saturated fatty acids with omega‐3 and omega‐6 fatty acids in daily diet reduces the risk of cardiovascular disease and prevents diseases such as Alzheimer's, bipolar disorder, and schizophrenia. Proper EPA and DHA content also help individuals with type 2 diabetes to reduce the elevated serum triacylglycerides. It also facilitates infants to reduce the risks of fatal myocardial infarction and other cardiovascular diseases. Hence, as recommended by the American Heart Association, it is necessary to consume fish, and especially oily fish at least twice per week as it is an excellent source of these fatty acids. Marine fishes of Salmonidae, Scombridae, and Clupeidae families are important sources of omega‐3 fatty acids but due to the increasing demand of PUFA and diminishing aquatic ecosystem, fishes are not a sustainable source to serve as a long‐term feed‐stock for omega‐3. Plants can synthesize some of PUFA such as oleic acid, LA, GLA (γ‐linolenic acid), ALA, and octadecatetraenoic acid but due to lacking some essential enzymes for PUFA synthesis such as desaturase and elongases, they are incapable of synthesizing EPA and DHA. Oleaginous microalgae and thraustochytrids could be a sustainable option to produce microbial EPA and DHA.
Article
Background: Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia. Objectives: To assess the effectiveness and safety of antiplatelet agents, such as aspirin and dipyridamole, when given to women at risk of developing pre-eclampsia. Search methods: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (30 March 2018), and reference lists of retrieved studies. We updated the search in September 2019 and added the results to the awaiting classification section of the review. Selection criteria: All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent were included. Studies only published in abstract format were eligible for inclusion if sufficient information was available. We would have included cluster-randomised trials in the analyses along with individually-randomised trials, if any had been identified in our search strategy. Quasi-random studies were excluded. Participants were pregnant women at risk of developing pre-eclampsia. Interventions were administration of an antiplatelet agent (such as low-dose aspirin or dipyridamole), comparisons were either placebo or no antiplatelet. Data collection and analysis: Two review authors assessed trials for inclusion and extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For this update we incorporated individual participant data (IPD) from trials with this available, alongside aggregate data (AD) from trials where it was not, in order to enable reliable subgroup analyses and inclusion of two key new outcomes. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. Main results: Seventy-seven trials (40,249 women, and their babies) were included, although three trials (relating to 233 women) did not contribute data to the meta-analysis. Nine of the trials contributing data were large (> 1000 women recruited), accounting for 80% of women recruited. Although the trials took place in a wide range of countries, all of the nine large trials involved only women in high-income and/or upper middle-income countries. IPD were available for 36 trials (34,514 women), including all but one of the large trials. Low-dose aspirin alone was the intervention in all the large trials, and most trials overall. Dose in the large trials was 50 mg (1 trial, 1106 women), 60 mg (5 trials, 22,322 women), 75mg (1 trial, 3697 women) 100 mg (1 trial, 3294 women) and 150 mg (1 trial, 1776 women). Most studies were either low risk of bias or unclear risk of bias; and the large trials were all low risk of bas. Antiplatelet agents versus placebo/no treatment The use of antiplatelet agents reduced the risk of proteinuric pre-eclampsia by 18% (36,716 women, 60 trials, RR 0.82, 95% CI 0.77 to 0.88; high-quality evidence), number needed to treat for one women to benefit (NNTB) 61 (95% CI 45 to 92). There was a small (9%) reduction in the RR for preterm birth <37 weeks (35,212 women, 47 trials; RR 0.91, 95% CI 0.87 to 0.95, high-quality evidence), NNTB 61 (95% CI 42 to 114), and a 14% reduction infetal deaths, neonatal deaths or death before hospital discharge (35,391 babies, 52 trials; RR 0.85, 95% CI 0.76 to 0.95; high-quality evidence), NNTB 197 (95% CI 115 to 681). Antiplatelet agents slightly reduced the risk of small-for-gestational age babies (35,761 babies, 50 trials; RR 0.84, 95% CI 0.76 to 0.92; high-quality evidence), NNTB 146 (95% CI 90 to 386), and pregnancies with serious adverse outcome (a composite outcome including maternal death, baby death, pre-eclampsia, small-for-gestational age, and preterm birth) (RR 0.90, 95% CI 0.85 to 0.96; 17,382 women; 13 trials, high-quality evidence), NNTB 54 (95% CI 34 to 132). Antiplatelet agents probably slightly increase postpartum haemorrhage > 500 mL (23,769 women, 19 trials; RR 1.06, 95% CI 1.00 to 1.12; moderate-quality evidence due to clinical heterogeneity), and they probably marginally increase the risk of placental abruption, although for this outcome the evidence was downgraded due to a wide confidence interval including the possibility of no effect (30,775 women; 29 trials; RR 1.21, 95% CI 0.95 to 1.54; moderate-quality evidence). Data from two large trials which assessed children at aged 18 months (including results from over 5000 children), did not identify clear differences in development between the two groups. Authors' conclusions: Administering low-dose aspirin to pregnant women led to small-to-moderate benefits, including reductions in pre-eclampsia (16 fewer per 1000 women treated), preterm birth (16 fewer per 1000 treated), the baby being born small-for-gestational age (seven fewer per 1000 treated) and fetal or neonatal death (five fewer per 1000 treated). Overall, administering antiplatelet agents to 1000 women led to 20 fewer pregnancies with serious adverse outcomes. The quality of evidence for all these outcomes was high. Aspirin probably slightly increased the risk of postpartum haemorrhage of more than 500 mL, however, the quality of evidence for this outcome was downgraded to moderate, due to concerns of clinical heterogeneity in measurements of blood loss. Antiplatelet agents probably marginally increase placental abruption, but the quality of the evidence was downgraded to moderate due to low event numbers and thus wide 95% CI. Overall, antiplatelet agents improved outcomes, and at these doses appear to be safe. Identifying women who are most likely to respond to low-dose aspirin would improve targeting of treatment. As almost all the women in this review were recruited to the trials after 12 weeks' gestation, it is unclear whether starting treatment before 12 weeks' would have additional benefits without any increase in adverse effects. While there was some indication that higher doses of aspirin would be more effective, further studies would be warranted to examine this.
Article
To evaluate uterine artery blood flow using pulsed Doppler, and endometrial and subendometrial microvascularization using three-dimensional (3D) power Doppler, in women with unexplained infertility. In a prospective clinical trial at a university teaching hospital, 40 women with unexplained infertility were compared to 40 fertile parous controls. In the mid-luteal (peri-implantation) phase, the endometrial thickness and volume, uterine artery pulsatility index (PI) and resistance index (RI), endometrial and subendometrial 3D power Doppler vascularization index (VI), flow index (FI), and vascularization flow index (VFI), and serum estradiol and progesterone levels were measured in both groups. The uterine artery PI (P=0.003) and RI (P=0.007) were significantly increased and the endometrial VI (P=0.029), FI (P=0.031), and VFI (P=0.001) and subendometrial VI (P=0.032), FI (P=0.040), and VFI (P=0.005) were significantly decreased in the unexplained infertility group. The endometrial thickness and volume and serum estradiol and progesterone levels, however, were not significantly different between the two groups. Peri-implantation endometrial perfusion is impaired in women with unexplained infertility: Doppler study of uterine hemodynamics should therefore be considered in infertility work-up.
Article
Full-text available
A total of 96 women undergoing in-vitro fertilization (IVF) treatment were examined by transvaginal ultrasonography with colour and pulsed Doppler ultrasound on the 22nd day of the menstrual cycle preceding IVF. We assessed endometrial thickness, endometrial morphology, myometrial echogenicity, subendometrial vascularization, the uterine artery pulsatility index, protodiastolic notch and end diastolic blood flow in order to define a uterine score which could be correlated with the pregnancy rate. The overall pregnancy rate was 30.2%, and there was no difference between the pregnant and non-pregnant groups with regard to any of the ultrasonographic and Doppler parameters when examined separately. However, the uterine score was significantly higher in the pregnant group (15.9 +/- 2.81 versus 12.7 +/- 5.3, P = 0.002; t-test). No pregnancy occurred if the score was between 0 and 10. With a score of 11-15 there was a 34.7% chance of pregnancy, and scores >16 had a 42% chance of pregnancy. In conclusion, individual ultrasonographic and Doppler parameters are not of sufficient accuracy to predict uterine receptivity. The uterine score calculated prior to IVF cycles appears to be a useful predictor of implantation.
Article
Full-text available
In Westernized societies, average consumption of n-6 polyunsaturated fatty acids (PUFAs) far exceeds nutritional requirements. The ratio of n-6 to n-3 PUFAs is generally >10:1 whereas on a primitive human diet it was closer to 1:1. Diets fed to intensively farmed livestock have followed a similar trend. Both n-6 and n-3 PUFAs can influence reproductive processes through a variety of mechanisms. They provide the precursors for prostaglandin synthesis and can modulate the expression patterns of many key enzymes involved in both prostaglandin and steroid metabolism. They are essential components of all cell membranes. The proportions of different PUFAs in tissues of the reproductive tract reflect dietary consumption. PUFA supplements (particularly n-3 PUFAs in fish oil) are promoted for general health reasons. Fish oils may also benefit fertility in cattle and reduce the risk of preterm labor in women, but in both cases current evidence to support this is inconclusive. Gamma-linolenic acid containing oils can alter the types of prostaglandins produced by cells in vitro, but published data to support claims relating to effects on reproductive health are lacking. Spermatozoa require a high PUFA content to provide the plasma membrane with the fluidity essential at fertilization. However, this makes spermatozoa particularly vulnerable to attack by reactive oxygen species, and lifestyle factors promoting oxidative stress have clear associations with reduced fertility. Adequately powered trials that control for the ratios of different PUFAs consumed are required to determine the extent to which this aspect of our diets does influence our fertility.
Article
Objective To compare the midluteal uterine artery impedance to blood flow as measured by the pulsatility index in women with different causes of infertility with that of women with normal fertility and to correlate this with endometrial thickness. Design A prospective study of normal women undergoing insemination with donor semen and subfertile women with tubal damage, endometriosis, premature ovarian failure, anovulation, or unexplained infertility. Setting A tertiary infertility center. Patients One-hundred sixty-one women (25 to 40 years of age) who were attending the clinic for subfertility treatment and 23 normal women who were having artificial insemination with donor sperm because their partners were azoospermic. Interventions All women were examined by transvaginal ultrasonography, with color flow imaging and blood flow analysis, on day 21 of an unstimulated ovarian cycle. Main Outcome Measures The mean pulsatility index of the left and right uterine arteries and the endometrial thickness. Results The patients were grouped according to the causes of infertility and compared with normal women. There were 23 women in the normal group (median pulsatility index, 1.91; range, 0.84 to 2.95), 35 with unexplained infertility (median pulsatility index, 2.45; range, 1.0 to 7.0), 91 with tubal damage (median pulsatility index, 2.65; range, 1.25 to 8.0), 8 with endometriosis (median pulsatility index, 2.32; range, 2.05 to 5.7), and 22 with anovulatory infertility (median pulsatility index, 3.03; range, 1.6 to 7.0). All the infertile groups had significantly different median pulsatility indexes when compared with the normal group, and the pulsatility indexes correlated with endometrial thickness. Conclusions The impedance to uterine artery blood flow is significantly different in women with different causes of infertility as compared with women of normal fertility. Increased resistance to uterine blood flow in the midluteal phase may be an important contributing factor to some causes of infertility and the cause of some previously “unexplained” infertility.
Article
Objective: To estimate the time course of human uterine artery vascular adaptation through the menstrual cycle into early pregnancy. Methods: We prospectively measured the uterine artery pulsatility index, peak systolic velocity, and volumetric blood flow during the menstrual cycle and at 4, 6, and 12 weeks of pregnancy in women who conceived. Upper extremity radial artery hemodynamic changes were examined as a control vessel. Ten subjects conceived within 12 months of menstrual cycle studies. Analyses were performed using repeated measures analysis of variance with P <.05 accepted for significance. Results: In women who conceived, uterine artery peak systolic velocity demonstrated a significant increase during the period of observation, which began after cycle day 10 (0.36 x 0.02 meters per second) of the menstrual cycle and continued though 12 menstrual weeks (1.05 +/- 0.10 meters per second, P <.001). Uterine artery pulsatility index decreased significantly during the observation window from 3.0 +/- 0.2 in the follicular phase to 1.6 +/- 0.2 at 12 menstrual weeks (P <.001). Blood flow in the uterine artery increased significantly from cycle day 10 (22.2 +/- 1.8 mL per minute) to 12 menstrual weeks' gestation (150.2 +/- 40.3 mL per minute, P <.001). These patterns were significantly different from the patterns observed for the radial artery. Conclusion: Uterine artery hemodynamic adaptation in early pregnancy follows a continuum established during the menstrual cycle. These adaptations result in decreased uterine artery impedance and increased blood flow. These changes differ from those observed in the upper extremity radial artery (control vessel) suggesting independence of regional pelvic and systemic hemodynamic adaptations.
Article
Omega-3 fatty acids (omega-3 FA) are constituents of the membranes of all cells in the body and are precursors of locally produced hormones, eicosanoids, which are important in the prevention and treatment of various diseases, especially in women. Omega-3 FA are of interest in some of the most common conditions affecting women. One mechanism underlying dysmenorrhea is a disturbed balance between antiinflammatory, vasodilator eicosanoids derived from omega-3 FA and proinflammatory, vasoconstrictor eicosanoids derived from omega-6 FA. Increased intake of omega-3 FA can reverse the symptoms in this condition by decreasing the amount of omega-6 FA in cell membranes. An increased prostacyclin/thromboxane ratio induced by omega-3 FA can facilitate pregnancy in women with infertility problems by increasing uterine blood flow. Supplementation with omega-3 FA during pregnancy lowers the risk of premature birth and can increase the length of pregnancy and birth weight by altering the balance of eicosanoids involved in labor and promote fetal growth by improving placental blood flow. Intake of omega-3 FA during pregnancy and breast feeding may facilitate the child’s brain development. There is also some evidence that supplementation with omega-3 FA might help to prevent preeclampsia, postpartum depression, menopausal problems, postmenopausal osteoporosis, and breast cancer. Furthermore, because elevated triglyceride levels are associated with cardiovascular disease, especially in women; and because omega-3 FA have powerful effects on triglycerides, women in particular gain from an increased intake of these fatty acids. This is especially important in women receiving hormone therapy, which can increase triglyceride levels. The quality of the omega-3 FA preparation is important. It should have an appropriate antioxidant content not to induce lipid peroxidation, and its content of dioxin and polychlorinated biphenyls (PCBs) should be well below the established safe limit. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to describe the function and actions of omega-3 and omega-6 fatty acids, to outline the potential advantages of omega-3 fatty acid supplementation, and to list the potential sources of omega-3 fatty acids.
Article
Objective To test the postulated preventive effects of dietary n-3 fatty acids on pre-term delivery, intrauterine growth retardation, and pregnancy induced hypertension.Design In six multicentre trials, women with high risk pregnancies were randomly assigned to receive fish oil (Pikasol) or olive oil in identically-looking capsules from around 20 weeks (prophylactic trials) or 33 weeks (therapeutic trials) until delivery.Setting Nineteen hospitals in Europe.Samples Four prophylactic trials enrolled 232, 280, and 386 women who had experienced previous pre-term delivery, intrauterine growth retardation, or pregnancy induced hypertension respectively, and 579 with twin pregnancies. Two therapeutic trials enrolled 79 women with threatening pre-eclampsia and 63 with suspected intrauterine growth retardation.Interventions The fish oil provided 2.7 g and 6.1 g n-3 fatty acids/day in the prophylactic and therapeutic trials, respectively.Main outcome measures Preterm delivery, intrauterine growth retardation, pregnancy induced hypertension.Results Fish oil reduced recurrence risk of pre-term delivery from 33% to 21% (odds ratio 0.54 (95% CI 0.30 to 0.98)) but did not affect recurrence risks for the other outcomes (OR 1.26; 0.74 to 2.12 and 0.98; 0.63 to 1.53, respectively). In twin pregnancies, the risks for all three outcomes were similar in the two intervention arms (95% CI for the three odds ratios were 0.73 to 1.40, 0.90 to 1.52, and 0.83 to 2.32, respectively). The therapeutic trials detected no significant effects on pre-defined outcomes. In the combined trials, fish oil delayed spontaneous delivery (proportional hazards ratio 1.22; 1.07 to 1.39, P= 0.002).Conclusions Fish oil supplementation reduced the recurrence risk of pre-term delivery, but had no effect on pre-term delivery in twin pregnancies. Fish oil had no effect on intrauterine growth retardation and pregnancy induced hypertension, affecting neither recurrence risk nor risk in twin pregnancies.
Article
Populations that consume a diet rich in marine lipids may have a lower risk of atherosclerotic disease. Fish oil contains the N-3 polyunsaturated fatty acid eicosapentaenoate, and the biosynthesis of thromboxanes and prostacyclins from eicosapentaenoate (thromboxane A3 and prostaglandin I3), rather than from the usual precursor arachidonate (thromboxane A2 and prostaglandin I2), may help to reduce the risk. To examine this hypothesis, we studied the effect of eicosapentaenoate supplementation (10 g per day) for one month on the synthesis of thromboxanes and prostacyclins, as assessed by urinary metabolite excretion, in six patients with peripheral vascular disease and seven normal controls. Supplementation markedly increased the eicosapentaenoate content of phospholipids from red cells and platelets. Synthesis of the platelet agonist thromboxane A2, which was elevated in the patients at base line, declined by 58 percent during supplementation but did not reach normal values. The decline in thromboxane A2, which is synthesized from arachidonate, coincided with the formation of the inactive thromboxane A3, which is synthesized from eicosapentaenoate. A lower dose of eicosapentaenoate (1 g per day) was not sufficient to maintain the changes in thromboxane A2 synthesis. Platelet function was only moderately inhibited during eicosapentaenoate supplementation, consistent with incomplete suppression of thromboxane A2 synthesis. These studies show that a high dose of eicosapentaenoate alters the pattern of synthesis of thromboxanes and prostacyclins. However, effects comparable to those of aspirin require long-term administration in high doses. Whether other properties of fish oil might render it a more attractive antithrombotic therapy remains to be determined.
Article
The objective of this long-running study was to determine whether the addition of low-dose aspirin to a standard hormone replacement therapy (HRT) protocol improved uterine perfusion during assisted conception. A total of 99 women scheduled for frozen embryo replacement were studied. Endometrial preparation was with a standard buserelin/HRT protocol. Uterine perfusion was assessed by Doppler ultrasound and classified as impaired or normal. In their first attempts, those with impaired perfusion (group I, n = 37) received low doses of aspirin [150 mg (n = 26) or 300 mg daily (n = 11)], starting from day 13 of HRT. Women with normal perfusion (group II) did not receive aspirin. In subsequent attempts, those from group I were arbitrarily allocated to start aspirin on day 1 or day 13 of HRT, and 10 women from group II were arbitrarily selected to receive aspirin from day 1 of HRT. In group I, the cancellation (46 versus 36%) and pregnancy rates (15 versus 25%) in those who received 150 or 300 mg aspirin daily were similar. In those with cancelled first attempts, good perfusion was achieved in 82 versus 20% (P < 0.02) of subsequent attempts using aspirin from day 1 versus day 13 of HRT. Higher pregnancy rates (47 versus 17%) were achieved in those taking aspirin from day 1 of HRT. In group II, pregnancy rates were not statistically different in those who did or did not receive aspirin during their subsequent attempts (10 versus 35%). The addition of low-dose aspirin to a standard HRT protocol in women with impaired uterine perfusion is associated with improved blood flow and satisfactory pregnancy rates.
Article
Since 1989, 22 patients with persistent antiphospholipid syndrome (PAPS) associated with recurrent miscarriage (defined as three or more miscarriages) were treated with fish oil, equivalent to 5.1 g eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a ratio of 1.5 EPA to DHA. Twenty-two patients had 23 pregnancies (one patient had two pregnancies) over a period of 3 years. There was only one intrauterine fetal death at the 27th week associated with pre-eclampsia. Twenty-one pregnancies, 19 of which ended after the 37th week, produced a baby. Two pregnancies ended with cesarean section for pre-eclampsia at 30th and 35th week of gestation and one is ongoing at 32nd week. All babies are well. The weight at birth of babies delivered at term was always > 2500 g. These encouraging results favour a therapeutic role, without any adverse reaction, of fish oil to prevent recurrent miscarriage in PAPS.
Article
High-dose supplements of fish oil reduce thromboxane synthesis in nonpregnant human subjects and were therefore proposed as a means of preventing various small-vessel disorders, including preeclampsia. The effect of fish oil on thromboxane metabolism in pregnancy was investigated in our study. Sixteen normal pregnant women in the third trimester of pregnancy were treated with a daily ingestion of 6 gm fish oil capsules containing 1.6 gm of n-3 fatty acid. In five patients the treatment was stopped because of severe-flavored reflux and hiccups. Eleven patients completed 3 weeks of treatment. Twenty-four-hour urinary 11-dehydro-thromboxane B2 was measured by means of radioimmunoassay before and after completion of the study protocol in these 11 patients and in seven control pregnant women who did not receive the oil treatment. A decrease ranging from 32% to 71%, in 24-hour urinary 11-dehydro-thromboxane B2 excretion (mean reduction from 1606 pg/mg creatinine to 779 pg/mg creatinine, p < 0.001) was found among the 11 fish oil-treated women. No change in excretion was found among the control women. No maternal, fetal, or neonatal bleeding disturbances occurred, and no laboratory changes in coagulation markers were observed. High-dose n-3 fatty acid intake in pregnancy significantly reduces maternal thromboxane A2 synthesis. These results may provide a basis for a possible role of fish oil in managing patients at risk for preeclampsia.
Article
Nitric oxide is a potent vasodilator and is involved in several physiological events during the female reproductive cycle. The aim of this study was to determine the acute effects of a nitric oxide donor on ultrasound-derived indices of blood flow in the intact human uterus and ovaries during the follicular phase of the normal menstrual cycle. The plan was to perform an observational study of six healthy volunteers, recruited during days 9-12 from day 1 of the last menstruation. Subjects were scanned transvaginally, with B-mode and color Doppler imaging around 12.00, and 2 h after the application of a transdermal glyceryl trinitrate (GTN) patch 10 mg/24 h. The patch was then removed and the subjects were rescanned 2 h later. END-POINTS: The main outcome measures were the peak systolic velocity (PSV), time-averaged maximum velocity (TAMV) and the pulsatility index (PI) derived from flow velocity waveforms, in the left and right main uterine arteries, a radial artery and subendometrial vessels, and from vessels at the rim of the dominant ovarian follicle. One woman was scanned on day 9, two on day 10 and three on day 12 of the cycle. The median pretreatment values for endometrial thickness and follicular volumes were 7.2 mm (range 6.0-10.0 mm) and 3.1 ml (range 0.3-6.8 ml), respectively. GTN induced a significant (p < 0.05) increase in the PSV and TAMV in the subendometrial vessels in all subjects. There was a corresponding decrease in the PI in four cases. Changes in blood flow were reversible (50% of the changes in PSV, TAMV and PI were essentially reversed 2 h after the patch had been removed). In the uterine arteries, PSV and TAMV were significantly (p < 0.01) and progressively decreased with a concomitant significant (p < 0.01) increase in PI. There was also a tendency for the mean PI to decrease progressively in the vessels at the rim of the dominant follicle with decreased post-treatment values in four out of six subjects. GTN induces a reversible increase in subendometrial blood flow velocity during days 9-12 of the menstrual cycle. The expected circadian decrease in uterine artery blood flow seemed to be partly interrupted by GTN treatment. These data justify the implementation of randomized controlled studies to determine the potential beneficial effects of transdermal GTN on ovarian and uterine blood flow and function.
Article
The objective of the study was to evaluate, in patients with unexplained infertilty, the possible relationship between anticardiolipin antibodies and indices of uterine artery Doppler measurements. A total of 46 infertile women participated in the study and underwent ovarian stimulation. Transvaginal ultrasonography and colour Doppler were performed on the day of embryo transfer and patients were divided on the basis of pulsatility index (PI): group I, PI <2.5; group II, PI 2.5-3.0; and group III, PI >3.0. On the same day that Doppler analysis took place, peripheral blood was obtained and circulating anticardiolipin antibodies were assayed. The response to ovarian stimulation was similar in the three studied groups. No significant differences in oestradiol and ultrasonographic parameters were observed between the groups. A significant increase in anticardiolipin antibodies was observed in those patients with higher resistance to flow at the level of the uterine artery. A significant relationship was found between the uterine artery PI and anticardiolipin immunoglobulin G class (F = 14.35; P = 0.001), and immunoglobulin M class (F = 5.88; P = 0.020). It is concluded that, in unexplained infertility, anticardiolipin antibodies may be involved in uterine vascular modifications and that Doppler flow analysis of uterine arteries may be an important tool in the assessment and management of ovarian stimulation.
Article
To determine the effects of low-dose aspirin on ovarian response, uterine and ovarian blood flow velocity, and implantation and pregnancy rates in patients undergoing IVF. Prospective, randomized, double-blind placebo-controlled assay. Department of Reproductive Medicine, CER Medical Institute, Buenos Aires, Argentina. Two hundred ninety-eight infertile patients (mean [+/- SDI age, 35.6+/-4.09 years) undergoing IVF cycles. In the treatment group, 149 patients underwent controlled ovarian hyperstimulation and received a daily dose of 100 mg of aspirin. In the control group, 149 patients underwent controlled ovarian hyperstimulation in association with placebo. Number of follicles, number of oocytes retrieved, serum E2 levels, uterine and ovarian pulsatility index, cancellation rate, number of embryos transferred, and implantation and pregnancy rates. There were statistically significant differences between the treatment group and the control group, respectively, in the number of follicles (19.8+/-7.2 versus 10.2+/-5.3), number of oocytes retrieved (16.2+/-6.7 versus 8.6+/-4.6), serum E2 levels (2,923.8+/-1,023.4 versus 1,614.3+/-791.7 pg/mL), uterine pulsatility index (1.22+/-0.34 versus 1.96+/-0.58), ovarian pulsatility index (1.18+/-0.31 versus 1.99+/-0.56), pregnancy rate (45% versus 28%), and implantation rate (17.8% versus 9.2%). Low-dose aspirin treatment significantly improves ovarian responsiveness, uterine and ovarian blood flow velocity, and implantation and pregnancy rates in IVF patients.
Article
To test the postulated preventive effects of dietary n-3 fatty acids on pre-term delivery, intrauterine growth retardation, and pregnancy induced hypertension. In six multicentre trials, women with high risk pregnancies were randomly assigned to receive fish oil (Pikasol) or olive oil in identically-looking capsules from around 20 weeks (prophylactic trials) or 33 weeks (therapeutic trials) until delivery. Nineteen hospitals in Europe. Four prophylactic trials enrolled 232, 280, and 386 women who had experienced previous pre-term delivery, intrauterine growth retardation, or pregnancy induced hypertension respectively, and 579 with twin pregnancies. Two therapeutic trials enrolled 79 women with threatening pre-eclampsia and 63 with suspected intrauterine growth retardation. The fish oil provided 2.7 g and 6.1 g n-3 fatty acids/day in the prophylactic and therapeutic trials, respectively. Preterm delivery, intrauterine growth retardation, pregnancy induced hypertension. Fish oil reduced recurrence risk of pre-term delivery from 33% to 21% (odds ratio 0.54 (95% CI 0.30 to 0.98)) but did not affect recurrence risks for the other outcomes (OR 1.26; 0.74 to 2.12 and 0.98; 0.63 to 1.53, respectively). In twin pregnancies, the risks for all three outcomes were similar in the two intervention arms (95% CI for the three odds ratios were 0.73 to 1.40, 0.90 to 1.52, and 0.83 to 2.32, respectively). The therapeutic trials detected no significant effects on pre-defined outcomes. In the combined trials, fish oil delayed spontaneous delivery (proportional hazards ratio 1.22; 1.07 to 1.39, P = 0.002). Fish oil supplementation reduced the recurrence risk of pre-term delivery, but had no effect on pre-term delivery in twin pregnancies. Fish oil had no effect on intrauterine growth retardation and pregnancy induced hypertension, affecting neither recurrence risk nor risk in twin pregnancies.
Article
Endometrial growth is thought to depend on uterine artery blood flow and the importance of endometrial development on in-vitro fertilization (IVF) outcome has been previously reported. Nitric oxide (NO) relaxes vascular smooth muscle through a cGMP-mediated pathway and NO synthase isoforms have been identified in the uterus. Sildenafil citrate (Viagra), a type 5-specific phosphodiesterase inhibitor, augments the vasodilatory effects of NO by preventing the degradation of cGMP. In this preliminary report we describe the use of vaginal sildenafil to improve uterine artery blood flow and sonographic endometrial appearance in four patients with prior failed assisted reproductive cycles due to poor endometrial response. The uterine artery pulsatility index (PI) was measured in a mock cycle after pituitary down-regulation with Lupron. The PI was decreased after 7 days of sildenafil (indicating increased blood flow) and returned to baseline following treatment with placebo. The combination of sildenafil and oestradiol valerate improved blood flow and endometrial thickness in all patients. These findings were reproduced in an ensuing gonadotrophin-stimulated cycle. Three of the four patients conceived. Although greater numbers of patients and randomized evaluation are needed to validate this treatment, vaginal sildenafil may be effective for improving uterine artery blood flow and endometrial development in IVF patients with prior poor endometrial response.
Article
The aim of this study is to evaluate the role of mild thyroid abnormalities in recurrent spontaneous abortion, and to assess the effects of two different therapeutical protocols. A prospective study in the population of recurrent aborters with mild thyroid abnormalities, evaluating the obstetric outcome in 42 patients. Sixteen thyroid autoantibodies positive patients were treated with thyroid replacement therapy, while 11 patients received intravenous immunoglobulins (IVIG). Fifteen patients, characterized by negative antithyroid antibodies, and having underlying thyroid pathology, were treated with thyroid replacement therapy. Among patients with thyroid antibodies, 6 out of the 11 pregnancies (54.5%) treated with IVIG ended in live birth. In the thyroid supplementation group, 13 out of 16 pregnancies (81.2%) ended in live birth. Only one pregnancy loss occurred among patients with a mild underlying thyroid pathology treated with thyroid replacement therapy. Mild thyroid abnormalities are associated with an increased rate of miscarriage. This poor obstetrical prognosis seems to be related to an impaired thyroid adaptation to pregnancy. Thyroid replacement therapy appears to be more effective than IVIG in preventing a new miscarriage.
Article
To evaluate the influence of uterine artery impedance to blood flow on the day of embryo transfer for prediction of early pregnancy loss and obstetric outcome. The uterine artery pulsatility index (PI) and resistance index (RI) were evaluated prospectively by transvaginal Doppler in 102 infertile women, who conceived as the result of fresh or frozen embryo transfer. Uterine artery impedance to blood flow was compared to the obstetric outcome. The 111 treatment cycles studied resulted in 31 spontaneous abortions, four ectopic pregnancies, and 76 deliveries. There were no differences in uterine artery PI and RI (mean +/- SD) between cycles resulting in normal delivery (2.69 +/- 0.71 and 0.88 +/- 0.06) and those resulting in spontaneous abortion (2.71 +/- 0.67 and 0.88 +/- 0.05) or ectopic pregnancy (2.36 +/- 0.54 and 0.85 +/- 0.06). There were no differences in PI and RI between uncomplicated singleton pregnancies (2.74 +/- 0.78 and 0.88 +/- 0.06) and those developing intra-uterine growth restriction (IUGR), pregnancy-induced hypertension (PIH), or preterm birth (2.54 +/- 0.47 and 0.87 +/- 0.04, pooled data). Uterine artery PI and RI on the day of embryo transfer were unrelated to the risk of the pregnancy ending in spontaneous abortion or ectopic pregnancy. These values were of no value in the prediction of IUGR, PIH or preterm birth.
Article
The aim of this prospective study was to explore the relationship between the incidence of recurrent spontaneous abortions (RSA) and values of Doppler indices characterizing the uterine and ovarian flows in nonpregnant women with a history of primary and secondary RSA using color, power and pulsed Doppler transvaginal ultrasonography. A total of 19 healthy women as a control group A and 81 women with a history of RSA as a study group B were examined on the 21st day of a regular menstrual cycle. Our study demonstrated the presence of significantly decreased uterine and ovarian blood flows in women with primary and secondary RSA if more than 3 abortions had occurred. The obtained values were less favorable in the primary RSA compared with the secondary RSA cases.
Article
Uterine perfusion appears to regulate uterine receptivity. However, vascular changes in recurrent pregnancy loss (RPL) remain poorly studied. One hundred and twenty one women were enrolled into this study: normal women with sterility caused by male factor (control group: n = 72) and women with RPL (n = 49). Women with uterine anomaly, impaired glucose tolerance, abnormal thyroid function, or anti-phospholipid antibodies were excluded from the study. In the mid-luteal phase of a non-pregnant cycle, transvaginal pulsed Doppler ultrasonography of the uterine artery was performed. Uterine arterial pulsatility index (PI), endometrial thickness, serum estradiol, progesterone, and nitrite/nitrate concentrations were determined. In the RPL group, the PI in the uterine artery of women with antinuclear antibodies was significantly higher than that of women without antinuclear antibodies (P < 0.05). Among women without antinuclear antibodies, the mean (+/-SD) uterine artery PI in the RPL group (2.44 +/- 0.41) was also significantly higher than in the control group (2.19 +/- 0.40; P < 0.01). The PI was inversely correlated with serum progesterone levels (r = -0.47, P < 0.01). Elevated uterine arterial impedance is associated with RPL. Pulsed Doppler ultrasonography is useful in identifying women with unexplained RPL who have impaired uterine circulation.
Article
This study was undertaken to evaluate uterine perfusion, which regulates uterine receptivity, in women with recurrent pregnancy loss. We evaluated the blood flow resistance in the uterine arteries of 104 pregnant women at 4 to 5 weeks' gestation by transvaginal pulsed Doppler ultrasonography (control group, n = 52; and recurrent pregnancy loss group, n = 52). Blood tests for antinuclear and antiphospholipid antibodies were also performed. The uterine arterial pulsatility index in the recurrent pregnancy loss group was significantly higher than that in the control group. Women with antinuclear or antiphospholipid antibodies had an elevated pulsatility index in the uterine artery, which is prominent in women with recurrent pregnancy loss. Coagulopathy and vascular dysfunction caused by autoantibodies may impair uterine perfusion. However, the uterine arterial pulsatility index in the recurrent pregnancy loss group was significantly higher than that in the control group even among women without antinuclear antibodies or among women without antiphospholipid antibodies. This observation strongly suggests that the uterine artery pulsatility index may be an independent index for recurrent pregnancy loss. The introduction of pulsed Doppler ultrasonography has provided the means for noninvasive evaluation of uterine impedance and may identify patients with recurrent pregnancy loss associated with impaired uterine perfusion.
Article
To evaluate vascular changes and uterine perfusion in women with recurrent pregnancy loss. We measured plasma levels of adrenomedullin of 100 pregnant women in the midluteal phase of a nonpregnant cycle (control group: n = 62; recurrent pregnancy loss group: n = 38). We measured the pulsatility index (PI) in the uterine arteries by transvaginal pulsed Doppler ultrasonography at the same time. The plasma level of adrenomedullin in women with recurrent pregnancy loss (5.6 +/- 1.9, mean +/- standard deviation) was significantly higher (P >.001) than that in control women (3.6 +/- 1.7). Uterine arterial PI of women with recurrent pregnancy loss (2.70 +/- 0.47) was significantly higher (P >.001) than that in control women (2.09 +/- 0.39). Plasma level of adrenomedullin had a significant positive correlation with uterine arterial PI both in the control group (r =.58, P <.001) and in the recurrent pregnancy loss group (r =.78, P <.001). Both plasma adrenomedullin concentration (7.2 +/- 2.3) and uterine arterial PI (3.06 +/- 0.36) were significantly high in women with antiphospholipid antibodies. Plasma adrenomedullin may serve as a useful biochemical marker for recurrent pregnancy loss caused by impaired uterine perfusion.
Article
To investigate changes in utero-ovarian blood flow during the peri-implantation period and their significance in successful embryo implantation. A prospective longitudinal study was conducted in 317 women undergoing in-vitro fertilization-embryo transfer (IVF-ET) treatment. All of them had at least one good-quality embryo for transfer on the second or third day after oocyte retrieval. Measurement of endometrial thickness and color flow imaging with pulsed waveform analysis of uterine and ovarian arteries were performed before ET and 5-6 days after ET. There were no significant differences in the age of patients, duration of infertility or number of embryos transferred between women who became pregnant (n = 91) and those who did not (n = 226). There was no difference in mean endometrial thickness between the two groups before ET, while a thicker endometrium was found in women who had conceived compared with those who had not 5-6 days after ET (P = 0.02). Mean uterine arterial resistance index (RI) and pulsatility index (PI) values were significantly lower in the pregnant than in the non-pregnant group before ET (P = 0.04 and P = 0.003, respectively), but no significant differences were found between the two groups 5-6 days after ET. In contrast, the mean ovarian arterial RI and PI values were similar between the two groups before ET, yet the pregnant group showed significantly lower RI and PI values compared with the non-pregnant group 5-6 days after ET (P = 0.002 and P = 0.01, respectively). A significantly higher peak systolic velocity (PSV) of intraovarian vessels was also noted in the pregnant group 5-6 days after ET. Different utero-ovarian blood flow changes during the peri-implantation period occur in conception and non-conception cycles in women following IVF. Doppler assessment of uterine arterial resistance can help to determine a time interval within the menstrual cycle that is of optimal endometrial status for embryo implantation in assisted conception programs. Delay in achieving adequate uterine perfusion during the temporal window of embryo implantation may have an impact on endometrial receptivity.
Article
Omega-3 fatty acids (omega-3 FA) are constituents of the membranes of all cells in the body and are precursors of locally produced hormones, eicosanoids, which are important in the prevention and treatment of various diseases, especially in women. Omega-3 FA are of interest in some of the most common conditions affecting women. One mechanism underlying dysmenorrhea is a disturbed balance between antiinflammatory, vasodilator eicosanoids derived from omega-3 FA and proinflammatory, vasoconstrictor eicosanoids derived from omega-6 FA. Increased intake of omega-3 FA can reverse the symptoms in this condition by decreasing the amount of omega-6 FA in cell membranes. An increased prostacyclin/thromboxane ratio induced by omega-3 FA can facilitate pregnancy in women with infertility problems by increasing uterine blood flow. Supplementation with omega-3 FA during pregnancy lowers the risk of premature birth and can increase the length of pregnancy and birth weight by altering the balance of eicosanoids involved in labor and promote fetal growth by improving placental blood flow. Intake of omega-3 FA during pregnancy and breast feeding may facilitate the child's brain development. There is also some evidence that supplementation with omega-3 FA might help to prevent preeclampsia, postpartum depression, menopausal problems, postmenopausal osteoporosis, and breast cancer. Furthermore, because elevated triglyceride levels are associated with cardiovascular disease, especially in women; and because omega-3 FA have powerful effects on triglycerides, women in particular gain from an increased intake of these fatty acids. This is especially important in women receiving hormone therapy, which can increase triglyceride levels. The quality of the omega-3 FA preparation is important. It should have an appropriate antioxidant content not to induce lipid peroxidation, and its content of dioxin and polychlorinated biphenyls (PCBs) should be well below the established safe limit.
Article
n-3 Fatty acids exert important effects on eicosanoid metabolism, membrane properties, and gene expression and therefore are biologically important nutrients. One n-3 fatty acid, docosahexaenoic acid, is an important component of neural and retinal membranes and accumulates rapidly in the brain and retina during the later part of gestation and early postnatal life. It is reasonable to hypothesize that maternal n-3 fatty acid intakes might have significant effects on several pregnancy outcomes as well as on subsequent infant visual function and neurodevelopmental status. Studies, both observational and interventional, assessing the influence of n-3 fatty acids during pregnancy or the early postpartum period on duration of gestation and infant size at birth, preeclampsia, depression, and infant visual function and neurodevelopment have been reported. n-3 Fatty acid intakes (both in terms of absolute amounts of docosahexaenoic acid and eicosapentaenoic acid and the ratio of these 2 fatty acids) varied widely in these studies, however, and no clear consensus exists regarding the effects of n-3 fatty acids on any of these outcomes. The available data suggest a modest effect of these fatty acids on increasing gestational duration and possibly enhancing infant neurodevelopment. Although data from earlier observational studies suggested a potential role of these fatty acids in decreasing the incidence of preeclampsia, this has not been confirmed in randomized, prospective trials. Because of the paucity of data from randomized, prospective, double-blind trials, the effect of n-3 fatty acids on depression during pregnancy or the early postpartum period remains unresolved.
Article
To compare the impedance to uterine artery blood flow, during the midluteal phase, in women with recurrent spontaneous abortion (RSA) as compared to normal fertile controls. A prospective study involving women with a history of RSA and fertile controls. University of Rome "Tor Vergata." Two hundred thirty women with RSA and 50 fertile controls referred for routine examination. Transvaginal Doppler examination of uterine arteries during the midluteal phase of untreated cycles. The mean pulsatility index (PI) of uterine arteries. Uterine arteries PI values in RSA patients (2.42 +/- 0.79) were significantly higher with respect to those found in the control group (2.08 +/- 0.47). When patients were grouped according to the different RSA causes, the highest PI values were found among patients with uterine abnormalities (2.82 +/- 1.0), antiphospholipid antibodies syndrome (2.70 +/- 1.1), and unexplained RSA (2.60 +/- 0.7). These values were significantly higher with respect to that found in the control group. No differences were observed in PI values between fertile patients and those with RSA due to thyroid abnormalities (2.10 +/- 0.55), inherited thrombophilia (2.03 +/- 0.45), autoimmune pathology (2.34 +/- 1.18), and genetic anomalies (2.47 +/- 0.54). Similar results were observed when patients were grouped according to primary and secondary RSA. Increased resistance to uterine blood flow may be an important contributing factor to some causes of RSA and may represent an independent indication of the risk of pregnancy loss.
Article
Recurrent pregnancy loss affects up to 5% of couples trying to establish a family. Evaluation classically begins after 3 consecutive miscarriages of less than 10 weeks of gestation but may be warranted earlier if a prior miscarriage was found to be euploid, or if there is concomitant infertility and/or advancing maternal age. The evaluation begins with an extensive history and physical, followed by a diagnostic screening protocol. Management must be evidence-based; unproven treatments should be avoided. If no factor is identified, many couples will still eventually have a successful pregnancy outcome with supportive therapy alone.
Article
To compare uterine artery pulsatility index (PI) and flow velocity wave (FVW) patterns between women with no history of abortion and women with recurrent pregnancy loss of unexplained cause. A cross-sectional study was conducted with 43 women with recurrent pregnancy loss and 43 women with no history of abortion and at least 1 child born at term (control group). Transvaginal ultrasonography with uterine artery Doppler evaluation was performed in the second phase of the menstrual cycle to calculate the PI and analyze the FVW pattern. The women with recurrent pregnancy loss had a significantly higher uterine artery PI than those in the control group (2.71+/-0.54 and 2.30+/-0.44, respectively), as well as a higher incidence of FVWs of the A and B types. Compared with the control group, a higher PI and a higher incidence of FVW of the A and B types--and thus a higher uterine artery impedance--were found among women with recurrent pregnancy loss.
Pregnancy outcome in women with inherited thrombophilias and recurrent spontaneous abortion treated with low molecular weight hepa-rin: preliminary results
  • E Vaquero
  • Di N Lazzarin
  • G Pierro
  • D Caserta
  • F Castaldo
  • H Valensise
Vaquero E, Lazzarin N, Di Pierro G, Caserta D, Castaldo F, Valensise H, et al. Pregnancy outcome in women with inherited thrombophilias and recurrent spontaneous abortion treated with low molecular weight hepa-rin: preliminary results. J Mat Fetal Neonatal Med 2003;13:40–3.
Aspirin and omega-3 in recurrent miscarriage
  • Lazzarin
300 Lazzarin et al. Aspirin and omega-3 in recurrent miscarriage Vol. 92, No. 1, July 2009