Tubal ectopic pregnancy: macrophages under the microscope

BACKGROUND: Ectopic pregnancy (EP) is a major reproductive health issue, whose underlying causes remain largely unknown. The unusual macrophage presence in the oviduct affected by EP could indicate macrophage contribution to the pathology. METHODS: Macrophages have important functions in reproduction that are reviewed in this work. They are needed for tissue remodelling and immune-regulatory roles, and are present both in the ovary and uterus. Numerous cytokines regulate monocytes recruitment, differentiation and function in the reproductive tract, among them leukaemia inhibitory factor (LIF), colony-stimulating factor 1 and transforming growth factor-beta are indispensable and non-redundant for reproductive outcome. Cytokine types and levels are modulated by estrogen, progesterone and seminal plasma, which drive the differentiation of monocytes to immunity cells or to immunosuppressed trophic and scavenging macrophages. RESULTS: Many risk factors for EP involve an inflammatory reaction that can induce the release of mononuclear phagocytes from the bone marrow and/or favour immunosuppressed trophic differentiation of newly recruited mononuclear phagocytes in the reproductive tract. These observations strengthen the hypothesis that immunosuppressed trophic and scavenging macrophages may have a role in EP onset. CONCLUSIONS: Macrophages may contribute to the regulation of tubal motility through prostaglandin production and induction of progesterone secretion. Considerations about LIF also suggest that macrophages may have a central role in ectopic receptivity.     

Evaluation of ectopic pregnancy by magnetic resonance imaging.

Patients (n = 37) suspected of ectopic pregnancy were prospectively evaluated with magnetic resonance (MR) imaging to assess the capability of MR imaging in the diagnosis of ectopic pregnancy. Five levels of confidence were defined: diagnostic, suspicious, equivocal, questionable, and negative. Tubal wall enhancement and presence of tubal haematoma or gestational sac-like structure were considered diagnostic findings. There were 21 diagnostic, two suspicious, eight equivocal, and six negative findings. MR findings were compared with the surgical findings in 18 patients. Surgical confirmation was obtained in 12 diagnostic, two suspicious, and four equivocal studies. Using the MR diagnostic criteria for tubal pregnancy, MR had 12 true positive, three true negative, three false negative, and no false positive results for the diagnosis of tubal pregnancy. Retrospective analysis of the signal intensity of haematoma and ascites was performed for these 18 surgically confirmed cases. The predominant signal intensity of tubal haematoma was an intermediate signal on T1-weighted image (WI) and a low signal on T2WI. Ascites showed signal intensity higher than that of urine on T1WI in 100% of 13 cases. In conclusion, MR imaging with use of intravenous contrast material allows a specific diagnosis of tubal pregnancy, recognizing tubal wall enhancement and fresh tubal haematoma.     

Microlaparoscopy for an intact ectopic pregnancy and endometriosis with the use of a diode laser: case report

Microlaparoscopy is a development of endoscopic surgery which further reduces invasiveness of surgical procedures. The use of a diode laser in microlaparoscopy for the treatment of a patient with an intact ectopic pregnancy and endometriosis is described for the first time. As the diode laser has easy management and widely recognized precision, its use could be highly advantageous in such situations. The success achieved in this case contributes to the wider use of micro-endoscopic procedures.     

Tubal ectopic pregnancy associated with an adenomatoid tumor

We present a case of coexistence of an ectopic pregnancy and an adenomatoid tumor in the same fallopian tube. The adenomatoid tumor is the most common benign neoplasm of the fallopian tube, and the vast majority of ectopic pregnancies occur in the fallopian tube. However, coexistence of these two conditions is extremely rare, and there has been only one previously reported case in the English literature. In the present case, the placental tissue, consisting of chorionic villi and decidua, was present in the ampulla, and the adenomatoid tumor was found in the myosalpinx, just proximal to the implantation site, replacing a large part of the myosalpinx. The close spatial relationship of these two lesions suggests that an adenomatoid tumor could have interfered with transportation of the fertilized ovum through the tube, possibly via impaired contractile activity of the myosalpinx, and consequently caused the ectopic tubal pregnancy.     

Pregnancy: Analysis of the risk factors with regard to the occurrence of ectopic pregnancy after medically assisted procreation

In a retrospective study (1985–1989) based on data fromthe Centre for Reproductive Medicine in Brussels, a total of23 ectopic pregnancies (2.24%) occurred after 3800 embryo, zygoteor gamete transfers. This number was low compared with the datapublished elsewhere. Tubal damage was a major risk factor towardsdeveloping an ectopic pregnancy after in-vitro fertilizationand embryo transfer. The number of ectopic pregnancies afterthe association of clomiphene citrate and human menopausal gonadotrophin(HMG) was significantly higher in patients with tubal (7.8%)and non-tubal indications (2.1%) compared with those stimulatedwith gonadotrophin-releasing hormone (GnRH) and HMG (2.18% and0.84%, respectively). The number of replaced embryos was notassociated with the rate of ectopic pregnancy and neither didtransfer technique (intra-uterine or intra-Fallopian transfer)influence the ectopic pregnancy rate.     

Ectopic pregnancy in a non-patent fallopian tube following transfer of embryos to the contralateral tube.

A case is reported of ectopic pregnancy in the non-patent leftFallopian tube after transfer of two pronuclear-stage embryosinto the right tube following in-vitro fertilization.     

Left ectopic pregnancy following gamete intra-fallopian transfer into the right fallopian tube: a report on two cases

Two cases are reported in which GIFT was performed into the right Fallopian tube, both resulting in ectopic pregnancy in the left Fallopian tube. The possible aetiological factors for the occurrence of contralateral ectopic pregnancy are discussed.     

eSET irrespective of the availability of a good-quality embryo in the first cycle only is not effective in reducing overall twin pregnancy rates

INTRODUCTION: In several clinics, elective single-embryo transfer (eSET) is applied in a selected group of patients based on age and the availability of a good-quality embryo. Whether or not eSET can be applied irrespective of the presence of a good-quality embryo in the first cycle, to further reduce the twin pregnancy rate, remains to be elucidated. METHODS: In patients <38 years two transfer strategies were compared, which differed in the first cycle only: group A (n = 141) received eSET irrespective of the availability of a good-quality embryo, and group B (n = 174) received eSET when a good-quality embryo was available while otherwise they received double embryo transfer (DET; referred to as eSET/DET transfer policy). In any subsequent cycle, in both groups the eSET/DET transfer policy was applied. RESULTS: After completion of their IVF treatment (including a maximum of three fresh cycles and the transfer of frozen-thawed embryos), comparable cumulative live birth rates (62.4% in group A and 62.6% in group B) and twin pregnancy rates (10.1 versus 13.4%) were found. However, patients in group A required significantly more fresh (2.0 versus 1.8) and frozen (0.8 versus 0.5) cycles. CONCLUSIONS: The transfer of one embryo in the first cycle, irrespective of the availability of a good-quality embryo, in all patients <38 years, is not an effective transfer policy for reducing the overall twin pregnancy rate.     

Pregnancy: Determinants of reproductive prognosis after ectopic pregnancy

The reproductive prognosis of 115 women desiring pregnancy whounderwent surgery for ectopic pregnancy between 1985 and 1990at the Clinica Luigi Mangiagalli, was analysed after a medianfollow-up period of 26 months (range 2–83). Probabilityof reproductive events was assessed by a product-limit model.Women who underwent surgery for ectopic pregnancy had a 54%probability of becoming pregnant (cumulative pregnancy rate,CPR) and a 36% probability of giving birth to a child (cumulativelivebirth rate, CLB) during the 3 years after surgery. Thesepercentages dropped with history of previous ectopic pregnancy(respectively 33%, P = 0.07, and 7%, P < 0.05). Increasingage at surgery and presence of adhesions in the contra-lateraltube seemed to be associated with poor reproductive prognosis(CPR = 40% and CLB = 12% for women aged 35 years and CPR = 37%and CLB = 20% in women with adhesions in the contra-lateraltube), but these findings were not statistically significant.No association emerged between fertility and parity or typeof surgery. The recurrence rate of ectopic pregnancy was 20%.No significant association emerged between recurrence of ectopicpregnancy and age, history of previous pregnancy, history ofprevious ectopic pregnancy, non-intact contra-lateral tube andsalpingotomy.     

Serum vascular endothelial growth factor as a possible marker for early ectopic pregnancy

BACKGROUND: This study evaluated serum vascular endothelial growth factor (VEGF) concentrations in women with normal intrauterine pregnancy (IUP), arrested IUP and ectopic pregnancy (EP). METHOD: This was a prospective, case-control study evaluating serum VEGF concentrations among 45 early pregnant women who subsequently were found to have an EP, a normal IUP or an arrested IUP (15 women in each group). Patients were stratified according to serum VEGF concentrations above and below 200 pg/ml. RESULTS: There was a significant difference in VEGF concentrations among women with EP, arrested IUP and normal IUP (306.1 +/- 26.5, 169.7 +/- 16.6 and 27.0 +/- 4.4 pg/ml respectively, P < 0.001). With a cut-off concentration of 200 pg/ml, serum VEGF could distinguish normal IUP from EP with a sensitivity of 88%, a specificity of 100% and a positive predictive value of 100%. Between EP and arrested IUP, the sensitivity was 87.5%, specificity 75% and positive predictive value of 77.8%. CONCLUSIONS: VEGF is a potential marker for EP. Its concentrations in women with EP are higher than in those with normal and arrested IUP.     

Return of reproductive performance after expectant management and local treatment for ectopic pregnancy.

The purpose of this study was to examine hysterosalpingographic findings and reproductive performance in patients previously managed non-surgically for ectopic pregnancy. Forty-nine patients with unruptured ectopic pregnancies were treated either by expectant management (n = 16) or medically (n = 33), using transvaginal methotrexate or sulprostone injection. The treatment was successful in 35 patients (71.5%), 12 out of 16 and 23 out of 33 in the two groups respectively. For all patients, follow-up currently varies from 3 to 52 months with a median follow-up of 16.6 +/- 11.2 months and 7.3 +/- 4.3 months in the two groups respectively. Hysterosalpingography was performed in 25 out of 26 patients who desired further pregnancy. We found evidence of tubal patency on the ectopic pregnancy treated side in 23 cases (92%). In this group, no recurrent ectopic pregnancy was observed. In the expectant management group, eight out of nine patients became pregnant, and the mean time to achieve pregnancy was 16.6 +/- 11.2 months. In the medical treatment group, eight out of 17 patients became pregnant and the mean time to achieve pregnancy was 8.6 +/- 4.2 months. In this last group, seven out of nine non-pregnant patients have had only a short follow-up, 4.5 +/- 3.2 months since treatment completion. No recurrent ectopic pregnancy was observed in this successfully treated group of patients who desired further pregnancy. We conclude that the medical approach to unruptured ectopic pregnancy is associated with a high rate of tubal patency and a reproductive performance similar to conservative surgical methods.     

Incidence of ectopic pregnancy. First results of a population-based register in France

A population-based register of ectopic pregnancy was establishedin 1992 for two French departments, with the primary aim ofmonitoring the trend in ectopic pregnancy over a prolonged period.In this paper, data collected pregnancy over a prolonged period.In this paper, data collected during the first year of registration(1992) are analysed. The rate of ectopic pregnancy was 20.2per 1000 live birth, 15.8 per 1000 reported pregnancies and9.5 per 10 000 women aged 15–44 years. The ectopic pregnancyrate per 1000 live births increased steeply after the age of30 years and especially after the age of 35 years, whereas ratesper 10 000 women of reproductive age steadily increased untilthe age of 35 years and decreased thereafter. The rates of ectopicpregnancy were lower in spring and summer than autumn and winter.These results are discussed and comparisions with similar studiesconducted in the USA and Scandinavia are attempted.     

Tubal curettage: a new conservative treatment for haemorrhagic interstitial pregnancies

Haemorrhagic interstitial pregnancies are commonly treated by cornual resection. This invasive procedure may increase the risk of uterine rupture in subsequent pregnancies. We report here a case of a haemorrhagic interstitial pregnancy, associated with a viable intrauterine pregnancy in a salpingectomized woman, which was treated successfully by curettage of the uterine cornu.     

Pregnancy: Cytogenetic characteristics of ectopic pregnancy

During a 12 month period, tissue was collected from 30 surgicallymanaged patients presenting with vital ectopic pregnancies.Chorionic villi of the removed tissue were successfully karyotypedby (semi-) direct chromosome technique in 22 cases. Only oneabnormal chromosomal complement, a triploidy (69,XXX) was found-As controls, 10 cases of intrauterine pregnancies were investigated,all showing a normal karyotype. These findings do not suggestan important role for chromosome abnormalities in the aetiologyof vital ectopic pregnancies.     

Pregnancy: Laparoscopy: a dispensable tool in the diagnosis of ectopic pregnancy?

Laparoscopy is regarded as the final decisive diagnostic testin suspected ectopic pregnancy. The new non-invasive diagnosticmethods of transvaginal sonography and serum human chorionicgonadotrophin (HCG) monitoring now challenge this pivotal roleof laparoscopy. In this prospective study the diagnostic valueof an algorithm, combining transvaginal sonography with an HCGcut-off level between 1000 and 1500 IU/I (IRP) was tested in208 consecutive women at risk for ectopic pregnancy. Three diagnosticcategories are designated by the algorithm: intra-uterine pregnancy(n = 73), ectopic pregnancy (n = 89), and trophoblast in regression(n = 46). The latter category represents patients in whom nopregnancy could be located by transvaginal sonography, withan initial HCG concentration < 1500 IU/I, declining duringfollow-up. The algorithm has a sensitivity of 0.97, a specificityof 0.95, a likelihood ratio for a positive test of 19.4, anda likelihood ratio for a negative test of 0.03. The describeddiagnostic strategy thus proved extremely reliable in the safemanagement of patients at risk for ectopic pregnancy, and renderslaparoscopy obsolete.     

Immunohistochemical analysis of oestrogen and progesterone receptors of eutopic and ectopic endometrium in the rabbit model of endometriosis: the effect of pregnancy.

Oestrogen receptors (ER) and progesterone receptors (PR) were measured in the rabbit model of endometriosis in eutopic and ectopic endometrium of pregnant animals (n = 7) and controls (n = 7). Immunostaining of cryostat sections of ectopic and eutopic endometrium was performed using monoclonal antibodies against ER and PR. Levels of ER and PR were 'evaluated' in a semi-quantitative manner using a modified histoscore. The ER and PR content in stromal and glandular cells was not different in eutopic and ectopic endometrium in either pregnant or non-pregnant control animals. There was a significant difference between the PR content of the glandular epithelium of pregnant animals and controls for both eutopic (P less than 0.02) and ectopic (P less than 0.001) endometrium. The disappearance of glandular PR and the persistence of stromal PR suggest that the function of the glandular endometrium is mediated by the paracrine and autocrine action of stromal cells. The decidual cells are likely to produce substances that may be of importance in embryo implantation and early pregnancy.     

Fertility after ectopic pregnancy: first results of a population-based cohort study in France

The purpose of this paper was to evaluate the reproductive outcomeafter ectopic pregnancy (EP) from a population-based registerin the centre of France. Since 1992, all the women aged 15–44years, who permanently reside in the target area and who weretreated either by surgical or medical procedures for an ectopicpregnancy in one of the area centres, have been registered andprospectively followed until 45 years of age. The analysis presentedwas based on the 155 women registered between January 1992 andMarch 1994 who were followed up for at least 6 months, and whowere seeking a new pregnancy. The mean follow-up period was16 months. A total of 102 women (66%) obtained a pregnancy.The first conception was intrauterine for 92 women, and 10 hada recurrence of ectopic pregnancy. Risk factors of recurrencewere prior spontaneous abortion and prior tubal damage. Forthose women who conceived, the mean time to obtain pregnancy(’time to pregnancy‘) was 4.8 months. The 1 yearcumulative intrauterine pregnancy rate (i.e. the probabilityof obtaining an intrauterine pregnancy within 1 year of seekingpregnancy) was 70%. After multivariate analysis by a Cox regression,the factors associated with higher fertility were age < 30years, high educational level and no prior tubal damage.     

Spontaneous conception and intrauterine pregnancy in a symptomatic missed abortion of ectopic pregnancy conceived in the previous cycle

We encountered a rare case of combined intrauterine and extrauterinepregnancy that occurred following separate spontaneous ovulations.A 33 year old woman visited our hospital with the chief complaintof abdominal pain on April 16, 1993. Her last menstruation wasfrom March 23 for 6 days. However, the urinary human chorionicgonadotrophin (HCG) on April 19 was 1024 IU/L Pelvic examinationand ultrasonography indicated an extrauterine pregnancy, whichwas confirmed by laparotomy and histo-logical identificationof trophoblast cells. The urinary HCG concentration markedlydecreased after the operation. However, the HCG level increasedagain on the fifth postoperative day, and a gestational sac(11 mm) was identified in the uterine cavity on the 11th post-operativeday, indicating that this intrauterine pregnancy was establishedfollowing spontaneous ovulation which occurred before the removalof the extrauterine pregnancy. This case indicates that a combinedpregnancy can occur not only after simultaneous multiple ovulationsbut also after the separate spontaneous ovulations.     

Pregnancy: Corpus luteum failure in ectopic pregnancy

The endocrinology of ectopic pregnancy was studied in orderto investigate the origin of the discordance in the circulatingamounts of human chorionic gonadotrophin (HCG) and those ofoestradiol and progesterone. Serial maternal blood samples wereobtained at 4–9 weeks gestation from 93 patients who becamepregnant following in-vitro fertilization and embryo transferincluding 10 ectopic, 21 anembryonic and 62 normal singletonpregnancies. The samples were analysed for HCG, Schwangerschaftprotein-1 (SP-1), pregnancy-associated plasma protein-A (PAPP-A),progesterone and oestradiol. In ectopic pregnancies, concentrationsof all substances analysed were significantly reduced comparedto singleton pregnancies from 5 weeks gestation (P < 0.05–0.001)but they were not significantly different from those of anembryonicpregnancies. In ectopic pregnancies, associations were foundbetween the concentration of both HCG and SP-1 and those ofprogesterone and oestradiol. No associations were found betweenPAPP-A and any other substances analysed. This may be due toinsensitivity of the PAPP-A assay; alternatively PAPP-A concentrationsmay be differentially reduced in ectopic pregnancy. These findingssuggest that progesterone and oestradiol are derived from thecorpus luteum in early ectopic pregnancy but that the corpusluteum fails rapidly and the dominant source of both hormonesbecomes the trophoblast as early as 5 weeks.