Partial tubal devascularisation: a novel procedure for tubal conservation in ectopic pregnancy.

Ectopic pregnancy is a serious condition that complicates 1-2% of pregnancies. Using surgical management is efficient, but may have an impact on future fertility. Although conservative tubal surgery has not been shown to have a significant advantage over a salpingectomy in terms of the future fertility potential, the conservative surgical techniques remain widely-utilised, particularly in the context of a contralateral diseased or absent tube. We hereby report a case series of a novel procedure to conserve the fallopian tube with the minimal risk of an incisional site bleeding through a partial segmental devascularisation. This technique seems to be an efficient method to minimise the intraoperative bleeding, limit the need for a blood transfusion, and yields a higher success rate of the procedure without jeopardising the blood supply and vitality of the tubes. Impact Statement What is already known on this subject? Conservative surgery has a significant value in women with a contralateral absent or diseased tube. However, a conservative management could be challenging due to the significant bleeding which can be encountered during the surgery. What the results of this study add? The partial devascularisation technique could achieve an adequate haemostasis by blocking the ascending blood supply only to the affected segment of the fallopian tube. What the implications are of these findings for clinical practice and/or further research? A partial devascularisation is a successful conservative surgical treatment option in most patients when the procedure is indicated.

Enhanced beta-catenin expression and inflammation are associated with human ectopic tubal pregnancy.

STUDY QUESTION: Is there a molecular link between Wnt signaling in fallopian tube inflammation and ectopic tubal implantation? SUMMARY ANSWER: Enhanced beta-catenin expression, reduced E-cadherin expression and glycogen accumulation in the tubal epithelia and hyperplasia in tubal arteries were found in ectopic tubal pregnancy, consistent with the effects induced by Wnt signaling and inflammation. WHAT IS KNOWN ALREADY: Chronic inflammation caused by infection can alter gene expression in the fallopian tube cells possibly leading to the development of ectopic pregnancy. Knockout mouse models have shown a relationship between Wnt/beta-catenin signaling and predisposition to tubal ectopic pregnancy. STUDY DESIGN, SIZE, DURATION: Women with ectopic tubal pregnancy (n = 18) were included in the case group, while women with chronic salpingitis (n = 13) and non-pregnant women undergoing sterilization procedures or salpingectomy for benign uterine disease (n = 10) were set as the controls. This study was performed between January 2012 and November 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: The ampullary segments of fallopian tubes were collected from patients. Tissues of tubal pregnancy were separated into implantation sites and non-implantation sites. Beta-catenin and E-cadherin expression were determined using immunohistological and immunofluorescence staining. Glycogen production was measured with periodic acid Schiff by staining. The diameter and wall thickness of tubal arteries were evaluated by histological analysis method. MAIN RESULTS AND THE ROLE OF CHANCE: Immunohistological staining revealed that beta-catenin protein expression was 100% positive in the ectopic pregnant and inflamed tubal tissues, and the staining intensity was significantly higher than in non-pregnant tubal tissues. In contrast, E-cadherin expression was reduced in ectopic pregnant fallopian tubes, possibly as a consequence of increased Wnt signaling. Moreover, glycogen accumulated in the tubal cells, and hyperplasia was observed in the tubal arteries with ectopic pregnancy, which is consistent with the effects induced by Wnt signaling and inflammation. All these changes could create the permissive environment that promotes embryos to ectopically implant into the fallopian tube. LIMITATIONS, REASONS FOR CAUTION: This finding requires a further confirmation about what activates Wnt signaling in ectopic tubal pregnancies. Also, it is generally recognized that Chlamydia infection is associated with ectopic pregnancy, and disturbs tubal epithelia via the Wnt signaling. However, the infection type in the samples used was salpingitis. WIDER IMPLICATIONS OF THE FINDINGS: A better understanding of the underlying mechanisms leading to ectopic pregnancies may contribute to our knowledge of the pathogenesis of tubal disorders and infertility and to the prevention of tubal ectopic pregnancy.

Arterial Blood Supply of the Mesosalpinx Appears Segmentally Organized in Absence of Uterine Tubes Arteries.

Arterial branches to the uterus and ovaries that pass through the mesosalpinx contribute significantly to the maintenance of the ovarian reserve. Especially arterial supply of the uterine tube is provided by a number of anastomoses between both the uterine and ovarian vessels. Knowledge on the morphologic peculiarities will allow to identify main contributors especially blood flow ultrasound examination for the purpose of ovary preserving surgery. This study aimed at identifying landmarks especially for so-called low-flow tubal vessels. Arteries of 17 female Thiel-embalmed bodies were studied along three preselected paramedian segments and measurements taken. A section was made through the center of the ovary perpendicular to uterine tube, then the mesosalpinx tissue distance was divided into 3 equivalent zones: upper, middle and lower thirds. The surface area of the mesosalpinx averaged 1088 ± 62 mm2. 47.7 ± 7.1 % of the mesosalpinx zones included macroscopically visible vessels. The lower third segment of mesosalpinx was the thickest averaging 2.4 ± 1.5 mm. One to three tubal branches were identified in the middle third of the mesosalpinx. Arterial anastomoses were found in the upper segment of the mesosalpinx, but no presence of a marginal vessel supplying the fallopian tube could be found. Statistically significant moderate positive correlations were established between the diameters of the mesosalpingeal arteries between the three zones. The mesosalpinx, uterine tube and the ovary form areas of segmental blood supply. Variants of tubal vessels appear to be a sparse source of blood supply.

Fertility after autologous ovine uterine-tubal-ovarian transplantation by vascular anastomosis to the external iliac vessels.

BACKGROUND: Transplantation of the uterus has been suggested as a treatment of uterine factor infertility. This study investigates whether the sheep uterus can resume its capacity to harbour normal pregnancies after autotransplantation by vascular anastomosis. METHODS: From 14 ewes, the uterus, excluding one uterine horn, was isolated along with its oviduct and ovary and preserved ex vivo and then transplanted back with end-to-side anastomosis of the vessels of the graft to the external iliac vessels. After recovery, the ewes underwent surgical examination and serum progesterone measurements to ascertain healing and ovarian activity. Afterwards, five autotransplanted and five control ewes were placed with a ram for mating. Caesarean sections were performed before the estimated term of pregnancy and data on fetal measures were compared. RESULTS: Of the 14 ewes, seven survived surgery with ovarian activity intact and grafts showing normal appearance. Mating occurred in four of five transplanted ewes and in five out of five controls, and three transplanted animals and five control animals conceived. In one transplanted ewe, torsion of the uterus was observed after spontaneous initiation of labour. Foeti from transplanted mothers were comparable in size to those of controls. CONCLUSIONS: Despite the encountered complications, this is the first report to demonstrate fertility and pregnancies going to term after autotransplantation of the uterus in an animal of a comparable size to the human.

Uterus transplantation in the baboon: methodology and long-term function after auto-transplantation.

BACKGROUND: Techniques for uterus transplantation (UTx) have been developed in rodent/domestic animals towards future clinical introduction of UTx to treat uterine factor infertility. The aim of this study was to extend the UTx research into a non-human primate species by developing surgical techniques for uterus retrieval and transplantation in the baboon. METHODS: Female baboons (n = 15) underwent surgery, with the initial five animals used for studies of pelvic vascular anatomy. Retrieval surgery included isolation of the ovarian veins and the uterine arteries together with the anterior branches of the internal iliacs. The utero-tubal-ovarian specimen was removed, flushed and kept ex vivo for 2 h when the two arterial ends and two venous ends were anastomosed side-to-side to construct one arterial and one venous end. These were, at auto-transplantation, anastomosed end-to-side to the external iliacs and the animals (n = 10) were evaluated concerning cyclicity and later by laparoscopy/laparotomy. RESULTS: The total duration of organ retrieval, backtable preparation and transplantation was around 6 h with an overall ischaemic time of the specimen of about 3 h. One animal died due to cardiomyopathy. Five out of the nine surviving animals resumed cyclicity, as a sign of re-established ovarian function. Only two out of these five animals exhibited resumed menstruation, indicating re-established ovarian and uterine function. Laparoscopy confirmed normal-sized uteri in these two animals. CONCLUSIONS: This study demonstrates the feasibility of UTx by vascular anastomosis in a non-human primate species. The low success rate demonstrates the complexity involved in UTx surgery and the need for further methodological developments.

Immunolocalization of aquaporin 1, 5, and 9 in the female pig reproductive system.

Thirteen mammalian aquaporin (AQP) isoforms have been identified, and they have a unique tissue-specific pattern of expression. AQPs have been documented in the reproductive system of both male and female humans, rats, and mice. However, tissue expression and cellular and subcellular localization of AQPs are unknown in the female reproductive system of pigs. In this study, AQP1 immunoreactivity was detected in the capillary endothelium of the ovary. Distinct immunolabeling of capillary endothelium was also observed in the oviduct and uterus. AQP5 was expressed in flattened follicle cells of primordial follicles, granulosa cells of developing ovarian follicles, and muscle cells of the oviduct and uterus. Staining of AQP5 was also observed in the epithelial cells of the oviduct and uterine epithelium. AQP9 immunoreactivity was observed in granulosa cells of developing follicles. AQP9 was also localized in the luminal epithelial cells of the oviduct and uterine epithelia cells. This is, to our knowledge, the first study that shows tissue expression and cellular and subcellular localization of AQPs in the reproductive system of the female pig. Moreover, these results suggest that several subtypes of the AQPs (AQP1, 5, and 9) are involved in regulation of water homeostasis in the reproductive system of gilts.

[Fallopian tube torsion--a rare complication in the reproductive age].

Isolated fallopian tube torsion (ITT) is a rare condition defined as a total or partial rotation of the fallopian tube around its vascular axis. The torsion initiaLLy interferes with the venous and lymphatic circulation. If unrelieved in time, rapid progression occurs, occluding the arterial circulation and Leading to gangrene and hemorrhagic necrosis. The cLinicaL appearance usually includes sharp lower abdominal pain, with or without peritoneal signs. Urinary and gastrointestinal signs might also occur. isolated fallopian tube is a rare condition; the incidence s estimated to be 1:500,000 mostly in reproductive age women. ITT is most common in the right side, although several reports claim that there is no difference between the sides. The etiology is not completely understood, but tubal anomalies (anatomic or physiologic) as well as trauma or pelvic inflammation are predisposing factors. The clinical appearance and the imaging in these cases are not pathognomonic, and many cases are delayed by means of diagnosis and treatment. The treatment is surgical. Detorsion or salpingectomy is usually performed by laparoscopy. Three cases that were treated lately at the Department of Obstetrics and Gynecology at the Hadassah Medical Center are presented together with a review of the literature.

Effect of nano-particles on MHD flow of tangent hyperbolic fluid in a ciliated tube: an application to fallopian tube.

This study shows the effects of magnetic field and copper nanoparticles on the flow of tangent hyperbolic fluid (blood) through a ciliated tube (fallopian tube). The present study will be very helpful for those patients who are facing blood clotting in fallopian tube that may cause for infertility or cancer. The nanoparticles and magnetic field are very helpful to break the clots in blood flowing in fallopian tube. Since blood flows in fallopian tube due to ciliary movement, therefore medicines containing copper nanoparticles and magnetic field with radiation therapy help to improve the patient. Ciliary movement has a particular pattern of motion i.e., metachronal wavy motion which helps to fluid flow. For the forced convective MHD flow of tangent hyperbolic nano-fluid, momentum and energy equations are solved by the small Reynolds' number approximation and Adomian decomposition method by constructing the recursive relation of ADM and solved by software "MATHEMATICA". The effects of parameters such as nanoparticle volume fraction, Hartmann number, entropy generation and Bejan's number have been discussed through graphs plotted in software "MATHEMATICA". It is found that blood flow is accelerated and heat transfer enhancement is maximum in the presence of nano particles, also magnetic effects accelerates the blood flow and help to enhance the heat transfer whereas the presence of porous medium increases the fluid's velocity and reduce the transfer of heat through fluid flow.

Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis.

Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific mitogen. To evaluate whether VEGF may play a role in angiogenesis, we have determined the spatial and temporal patterns of expression of VEGF and VEGF receptors during natural angiogenic processes taking place within the female reproductive system. Four angiogenic processes were analyzed: neovascularization of ovarian follicles, neovascularization of the corpus luteum, repair of endometrial vessels, and angiogenesis in embryonic implantation sites. During all processes, VEGF mRNA was found to be expressed in cells surrounding the expanding vasculature. VEGF was predominantly produced in tissues that acquire new capillary networks (theca layers, lutein cells, endometrial stroma, and the maternal decidua, respectively). VEGF-binding activity, on the other hand, was found on endothelial cells of both quiescent and proliferating blood vessels. These findings are consistent with a role for VEGF in the targeting of angiogenic responses to specific areas. Using in situ hybridization, we show that VEGF is expressed in 10 different steroidogenic and/or steroid-responsive cell types (theca, cumulus, granulosa, lutein, oviductal epithelium, endometrial stroma, decidua, giant trophoblast cells, adrenal cortex, and Leydig cells). Furthermore, in some cells upregulation of VEGF expression is concurrent with the acquisition of steroidogenic activity, and expression in other cell types is restricted to a particular stage of the ovarian cycle. These findings suggest that expression of VEGF is hormonally regulated. We propose that excessive expression of VEGF during gonadotropin-induced ovulation may contribute to the development of ovarian hyperstimulation syndromes by virtue of the vascular permeabilization activity of this factor.

Tuba-ovarian auto-amputation caused by ovarian teratoma in an adolescent girl.

Atici A, Yilmaz E, Karaman A, Apaydin S, Afsarlar ÇE. Tuba-ovarian auto-amputation caused by ovarian teratoma in an adolescent girl. Turk J Pediatr 2017; 59: 90-92. Ovarian auto-amputation is an extremely rare condition commonly encountered in the perinatal period. Spontaneous or secondary torsion of the ovary caused by an ovarian lesion may result in infarction and subsequent auto-amputation of the ovary. This paper demonstrates a case that underwent laparoscopic appendectomy with an incidental calcified auto-amputated right ovary. A 16-year-old adolescent girl was admitted to our department with a history of one-day abdominal pain. Physical examination of the patient revealed abdominal tenderness and rigidity on right lower quadrant. Her white blood cell count was 11x103/mL, and C-reactive protein was 69 mg/L. The patient underwent a laparoscopic appendectomy with a provisional diagnosis of acute appendicitis, and further exploration revealed a 2x2 cm white ovoid mass floating freely in the pelvis. The left ovary was clearly identified in its usual localization, but the right tuba was blindly ending without any fimbria or ovary. Postoperative course of the patient was uneventful, and she was discharged on postoperative day 2. The histopathological examination revealed a necrotic calcified ovarian teratoma. Auto-amputated ovary is a rare occasion mostly encountered during perinatal period, and it may be unilateral or bilateral. An auto-amputated ovarian mass may rarely be a teratoma although the most common cause of auto-amputation during perinatal and adolescent period is ovarian torsion due to an ovarian cyst.

Quantitative evaluation of the vasculature supplying the oviduct in pre-pubertal and sexually mature sows.

The present work was aimed at characterizing the regional vascularization of the oviduct in the pig to ascertain whether the number of terminal mesosalpingeal arterioles supplying the isthmus and ampulla is influenced by reproductive maturity and state of the estrous cycle. The total number of terminal arterioles (NTA) in the mesosalpinx was quantified under a stereomicroscope in latex injected ex-vivo reproductive tracts from pre-pubertal (n = 10) and mature sows (n = 34), the latter allocated into three phases of the estrous cycle: follicular (n = 12); early luteal (n = 11); and late luteal (n = 11). The NTA and density of terminal arterioles (DTA) changed little between pre-pubertal and mature sows or among sows of different reproductive status (P > 0.05). Conversely, both in pre-pubertal and mature sows the isthmus showed higher DTA (P < 0.001) than the ampulla. It is concluded that the pattern of vascularization supplying the porcine oviduct is essentially established before the onset of puberty so that neither cyclical changes coupled with the estrous cycle nor regional variations between the isthmus and ampulla are likely at the level of the terminal arterioles supplying the oviduct during the reproductive life.

Novel coexpression of human chorionic gonadotropin (hCG)/human luteinizing hormone receptors and their ligand hCG in human fallopian tubes.

The human uterus, including its blood vessels, contains hCG/human LH receptors. We now demonstrate that human fallopian tubes also contain a 4.4-kilobase hCG/LH receptor mRNA transcript and an 80-kilodalton immunoreactive protein that can bind [125I]hCG. Tubal mucosa contain more receptor transcripts, receptor protein, and [125I] hCG binding than the tubal smooth muscle or blood vessels. Human fallopian tubes also contain hCG protein and a 0.6-kilobase hCG alpha mRNA transcript. However, very little hCG is found in tubal cell layers other than mucosa. Ampullary segments contain more hCG/LH receptors and hCG than isthmus. Secretory phase tubes contain more than proliferative phase, postpartum, or postmenopause tubes. Incubation with highly purified hCG resulted in an increase in catalytically active 5-lipoxygenase, cyclooxygenase-1, and cyclooxygenase-2 enzymes in tubal tissues. In summary, human fallopian tubes, which have never previously been considered a direct target of hCG/LH action, express functional hCG/LH receptor gene as well as the gene of its ligand. These novel findings suggest numerous possibilities of both physiological and pathological importance in human fallopian tubes.

Involvement of adrenoceptors in the ovarian vascular pedicle in the regulation of counter current transfer of steroid hormones to the arterial blood supplying the oviduct and uterus of pigs.

1. On Day 10 of the oestrous cycle in pigs, after laparotomy noradrenaline (NA), methoxamine (alpha 1-adrenomimetic, M), Prazosin (alpha 1-adrenolytic, Pr) in total doses of 4 mumol, and saline were infused (10 min) into the superficial layer of mesovarium on both sides of the ovarian pedicle vasculature, close to the ovary. 2. Blood flow in the ovarian artery, heart rate and progesterone (P4) and androstenedione (A4) secretion from the ovary and their concentrations in the ovarian venous effluent, as well as the concentrations of P4 and A4 in the blood supplying the oviduct and the uterus, were determined. 3. A significant increase of P4 and A4 secretion after NA and M infusion and increased concentrations of P4 and A4 in the ovarian venous effluent were found, but these changes did not influence the counter current transfer of hormones from the venous effluent into arterial blood supplying the oviduct and the uterus. 4. Infusion of Pr caused a significant decrease of P4 and A4 secretion and their concentrations in the ovarian venous effluent and significantly increased A4 concentration in the blood supplying the oviduct and uterus. 5. The results indicate that stimulation of alpha 1-adrenoceptors in the area of ovarian vasculature did not influence, whereas block of alpha 1-adrenoceptors affected, the local concentration of steroid hormones in the blood supplying the oviduct and the part of the uterus proximal to the ovary, despite the changes in the concentrations of steroid hormones in the ovarian effluent.

Characterization of postsynaptic alpha-adrenoceptors in the arteries supplying the oviduct.

1. In vitro experiments were designed to characterize postjunctional alpha-adrenoceptor subtypes in ring segments (1 mm length; outer diameter 300-500 microns) from arteries supplying the oviduct of the heifer. 2. Noradrenaline, adrenaline and phenylephrine evoked concentration-dependent contractile responses. The pD2 values were 5.67, 5.89 and 5.93, respectively. Medetomidine clonidine and B-HT 920 (2-amino-6-allyl-5,6,7,8-tetra-hydro-4H-(thiazo)-4,5-d-azepoine ) were ineffective. 3. The alpha-adrenoceptor selective antagonists, prazosin (1 nM-0.1 microM) and rauwolscine (0.1-10 microM) competitively antagonized the response to noradrenaline. The pA2 values were 9.38 and 6.83, respectively. 4. The dissociation constant (KD) for noradrenaline calculated by use of the irreversible antagonist, dibenamine, was 3.95 (2.09-5.81) microM. The occupancy-response relationship was non-linear. Half-maximal response to noradrenaline was obtained with 22% receptor occupancy while maximal response required 100% occupancy. 5. B-HT 920 evoked a biphasic contractile concentration-dependent response in preparations incubated in a physiological solution containing 20 mM K+, 0.1 microM prazosin and 1 microM propranolol. Rauwolscine 0.1 microM significantly (P less than 0.01) blocked the first component of the B-HT 920 concentration-response curve with an apparent pA2 value of 8.52 (7.86-9.18). 6. These results strongly suggest that alpha-adrenoceptors in oviductal arteries are mainly of the alpha 1 subtype, although a possible role for alpha 2-adrenoceptors cannot be excluded.

Endothelium-dependent relaxation to acetylcholine in bovine oviductal arteries: mediation by nitric oxide and changes in apamin-sensitive K+ conductance.

1. Mechanisms underlying the relaxant response to acetylcholine (ACh) were examined in bovine oviductal arteries (o.d. 300-500 microns and i.d. 150-300 microns) in vitro. Vascular rings were treated with indomethacin (10 microM) to prevent the effects of prostaglandins. 2. ACh elicited a concentration-related relaxation in ring segments precontracted with noradrenaline (NA), which was abolished by endothelium denudation. 3. The ACh-induced relaxation was attenuated but not abolished by NG-nitro-L-arginine (L-NOARG, 1 microM-1 mM), an inhibitor of nitric oxide (NO) formation. The inhibition caused by L-NOARG (10 microM) was reversed by addition of excess of L-arginine but not D-arginine (1 mM). 4. In high K+ (40-60 mM)-contracted rings, ACh was a much less effective vasodilator and its relaxant response was completely abolished by L-NOARG (100 microM). 5. In NA (10 microM)-contracted rings, ACh induced sustained and concentration-dependent increases in cyclic GMP, which were reduced below basal values by L-NOARG (100 microM), while potent relaxation persisted. Similar increases in cyclic GMP were evoked by ACh in high K+ (50 mM)-treated arteries and under these conditions, both cyclic GMP accumulation and relaxation were L-NOARG-sensitive. 6. S-nitroso-L-cysteine (NC), a proposed endogenous precursor of endothelial NO, also induced cyclic GMP accumulation in NA-contracted oviductal arteries. 7. Methylene blue (MB, 10 microM), a proposed inhibitor of soluble guanylate cyclase, inhibited both endothelium-dependent relaxation to ACh and endothelium-independent response to exogenous NO, whereas relaxation to NC remained unaffected. 8. The L-NOARG-resistant response to ACh was not affected by either ouabain (0.5 mM), glibenclamide (3 microM), tetraethylammonium (TEA, 1 mM) or charybdotoxin (50 nM), but was selectively blocked by apamin (0.1-1 microM). However, apamin did not inhibit either relaxation to ACh in high K(+)-contracted rings or endothelium-independent relaxation to either NO or NC. 9. Apamin and MB inhibited ACh-induced relaxation in an additive fashion, suggesting the involvement of two separate modulating mechanisms. 10. These results suggest that ACh relaxes bovine oviductal arteries by the release of two distinct endothelial factors: a NO-like substance derived from L-arginine, which induces cyclic GMP accumulation in smooth muscle, and another non-prostanoid factor acting by hyperpolarization mechanisms through alterations in apamin-sensitive K+ conductance.