Hormonal profiles of early gestations with abnormal karyotype

OBJECTIVE: To describe the hormonal profiles of chromosomally abnormal pregnancies during the first trimester. DESIGN: A prospective study from 1984 through 1990 in which infertility patients who conceived were monitored weekly with serum E2, P, and beta-hCG levels. SETTING: The infertility practice at Rush-Presbyterian-St. Luke's Medical Center in Chicago, Illinois. PATIENTS: Study included 15 women who had dilatation and curettage for first trimester fetal losses with confirmed abnormal karyotype, 6 women with chromosomally normal male abortuses, and 60 consecutive women whose pregnancies yielded normal term infants. RESULTS: After natural conception, E2 demonstrated a moderate rise in both normal and chromosomally abnormal pregnancies to approximately 300 pg/mL by day 29 (6 weeks of gestation). In normal gestations, E2 continued a steady increase to exceed the level of 1,000 pg/mL by day 64 (11 weeks of gestation). In chromosomally abnormal pregnancies, the mean E2 plateaued and remained at approximately 200 pg/mL until fetal demise was noted. In stimulated conceptions, the rise of E2 was sharp and early (1,200 pg/mL by day 29); in normal pregnancies, E2 steadily increased to an average of 1,400 pg/mL by the end of the first trimester, whereas in karyotypically abnormal gestations, E2 declined to approximately 200 pg/mL by day 64. In pregnancies yielding a male abortus, a sharp decline and plateau at 800 pg/mL by day 56 (10 weeks of gestation) was observed. In both natural and stimulated normal pregnancies, hCG levels first demonstrated a linear rise, followed by a curvilinear increase from day 29 until day 56, with a peak of approximately 110,000 mIU/mL. The beta-hCG in chromosomally abnormal pregnancies, as well as in pregnancies yielding a male abortus, was characterized by a slow and gradual rise to a maximum of 40,000 mIU/mL, which remained relatively linear until day 64 when fetal demise was detected in all cases. Progesterone level data were excluded from analysis because of frequent P supplementation. CONCLUSIONS: There were significant differences in the hormonal profiles of chromosomally normal and abnormal pregnancies. Serial measurements of serum E2 and beta-hCG from the 6th week of gestation may be useful in predicting an abnormal karyotype sooner than other current diagnostic tests.     

Late complications after systemic methotrexate treatment of unruptured ectopic pregnancies: a report of three cases

BACKGROUND: The use of methotrexate (MTX) by systemic administration in the treatment of unruptured ectopic pregnancy has been reported as a safe and effective method. CASES: We report three cases (one hematosalpinx and two pelvic hematocoeles) of complications after the use of MTX in the treatment of unruptured ectopic pregnancies. All three cases came to our observation for pelvic pain, abnormal bleeding and a pelvic mass after an interval of 3-5 months, subsequent to the disappearance of symptoms and normalization of serum human chorionic gonadotropin beta-subunit (beta-hCG) levels. CONCLUSIONS: These findings suggest that: (a) such complications should be considered before selecting the mode of treatment for ectopic pregnancy; and (b) that an early ultrasonographic control should be performed after MTX treatment even when the decline in beta-hCG levels suggests a successful resolution. This would permit an early diagnosis of these late complications.     

Prognostic factors for an unsatisfactory primary methotrexate treatment of cervical pregnancy: a quantitative review

To determine the risks when the primary methotrexate (MTX) treatment of cervical pregnancy has an unsatisfactory outcome, we conducted a Medline search on relevant literature published from January 1983 to June 1997. The search yielded 28 publications of 48 cases of cervical pregnancy. These and four new cases from our institutions were used in our study. A cervical pregnancy that presented with a serum beta-human chorionic gonadotrophin concentration of > or = 10,000 mIU/ml [odds ratio (OR) 10.82, 95% confidence interval (CI) 2.59, 45.14], gestational age at > or = 9 weeks (OR 6.44, 95% CI 1.46, 28.52), embryonic cardiac activity (OR 14.29, 95% CI 2.95, 76.92), and crown-rump length of >10 mm (OR 13.33, 95% CI 1.46, 120.48) was considered to be associated with a higher unsatisfactory rate of primary MTX treatment. A concomitant feticide was found to enhance the therapeutic effect of MTX treatment if embryonic cardiac activity was evident (OR 0.13, 95% CI 0.02, 0.68). Administration of a high dose of MTX did not seem to be more effective than a lower one. Our findings supported some previous observations and, more importantly, provided useful clinical information in selecting appropriate candidates for MTX treatment in cases of cervical pregnancy.     

Medical management of interstitial ectopic pregnancy: a case report and literature review

Recent reports describe successful treatment of interstitial ectopic pregnancies using methotrexate. While the number of reported cases is increasing, no consensus exists regarding the management of this complication of pregnancy. We present the successful use of combined systemic and direct intrasac injection of methotrexate for an interstitial pregnancy with the highest yet reported initial beta-human chorionic gonadotrophin concentration (102,000 mIU/ml). We also describe the use of Doppler ultrasound for monitoring treatment progression. Through a review of the current literature, we propose to facilitate management decisions and increase outcome success by summarizing previously reported treatment regimens and by describing enhanced parameters for patient selection and monitoring.     

Plasma albumin induces calcium waves in rat cortical astrocytes

At the end of the 19th century, ectopic pregnancy became a surgical procedure. A century later, one third of ectopic pregnancies are treated medically. In the meantime, early detection of ectopic pregnancy became possible due to sensitive serum hCG and progesterone combined assays with transvaginal sonography and a knowledge of risk factors. Consequently, a nonsurgical approach appears to be an attractive alternative to surgery. Expectant management is recommended with a plateau or decreasing hCG and an initial level < or = 1.000 mIU/ml in asymptomatic women. Medical treatment by local or parenteral methotrexate is recommended in patients with clear evidence of an unruptured pregnancy in based on initial hCG and progesterone level, size of hemoperitoneum, ultrasound diameter of hematosalpinx and absence of clinical pain. Laparoscopy remains the gold standard but in prospective randomized trials between medical treatment and laparoscopy, in selected patients, the non-surgical approach appears to be equivalent with a similar reproductive performance.     

Injection of 5-fluorouracil in the treatment of tubal pregnancy through salpingo-catheter under hysteroscopy

Seventeen women with unruptured tubal pregnancy were given 5-FU through salpingo-catheter under hysteroscopy. In one case the injection failed because the tube opening could not be found. The success rate of salpingo-catheterization was 94.12% (16/17). The cure rate for the tubal pregnancies was 88.24% (15/17). 12 cases received injection once and 3 cases twice. The dose of 5-FU per injection was 250 mg in 10 ml solution. Serum beta-hCG test became negative in 7 to 14 days after the treatment, and signs and symptoms disappeared. Salpingography were done in 8 cases after 2 to 3 months, and all the diseased tubes were found patient. There was little side effects due to this treatment, which is more effective, convenient and less traumatic than injecting 5-FU to the affected site through laparoscopy or systemic administration. It may turn out to be an effective, simple, safe and acceptable new method for treating early tubal pregnancy.     

Vascular patterns of gestational trophoblastic tumors by color Doppler ultrasound

BACKGROUND: Destruction of uterine vasculature is a common phenomenon in gestational trophoblastic tumors. The authors categorized such uterine vasculature by color Doppler ultrasound and studied its clinical significance. METHODS: Color Doppler ultrasound was performed in 28 patients with gestational trophoblastic tumors. The vascular morphologic manifestations were recorded, and the peak systolic velocity and resistance index of uterine artery were calculated. Serum beta-human chorionic gonadotropin (hCG) levels were measured periodically to monitor chemotherapy response. Seventeen uneventful postmole uteri were used as controls. Two-tailed Student's t-test and Fisher's exact test were used for statistical analysis. RESULTS: The gestational trophoblastic tumors were categorized as diffuse type (N = 7), lacunar type (N = 16), and compact type (n = 5) according to their vascular patterns. The mean serum beta-hCG level at diagnosis in diffuse type lesions (6608 +/- 6320 mIU/mL) was significantly lower than in the lacunar type (40462 +/- 39735 mIU/mL; P = 0.04) and compact type (212114 +/- 205126 mIU/mL; P = 0.02), whereas the level in compact type lesions was significantly higher than in the lacunar type (P = 0.003). Lacunar type lesions exhibited a significantly lower uterine artery resistance index (0.51 +/- 0.13) than diffuse type (0.66 +/- 0.10; P = 0.03) or compact type lesions (0.70 +/- 0.06; P = 0.02). All lesions exhibited significantly higher peak systolic velocity than control subjects (P < 0.001); however, no significant difference was observed among them. Brief courses (< 5 cycles) of chemotherapy cured more diffuse type (6 of 7) than lacunar type (3 of 15, P = 0.006) or compact type lesions (0 of 5, P = 0.008). Histopathologic diagnosis was available for 11 lesions. They were invasive mole in seven lacunar type lesions and choriocarcinoma in four compact type lesions. CONCLUSION: Vascular morphologic patterns of gestational trophoblastic tumors by color Doppler ultrasound correlated well with beta-hCG levels, uterine hemodynamics, chemotherapy response, and possibly the histopathologic diagnosis.     

Variability of cutaneous lymphatic flow rates in melanoma patients

A woman with a small (6-mm gestational sac) interstitial pregnancy had complete resolution after medical therapy alone. A single cycle of methotrexate 50 mg/m2 was used as outpatient treatment without any operative procedure either for diagnosis or intervention. The guidelines that have evolved for selection of women for single dose methotrexate treatment for both intrauterine and tubal ectopic pregnancies may be applicable to interstitial ectopic pregnancy as well. A suggested framework for treatment decisions is presented.     

Clinical characteristics of patients with rheumatoid arthritis and methotrexate induced pneumonitis

OBJECTIVE: To determine the clinical features of methotrexate (MTX) pneumonitis in patients treated for rheumatoid arthritis (RA). METHODS: The medical records of 284 patients with RA who had been treated with oral MTX (mean followup 33.2 mo) were reviewed retrospectively. RESULTS: MTX induced interstitial pneumonitis developed in 6 patients (2.1%). The affected patients were significantly older than those without MTX pneumonitis (67.3 +/- 9.8 vs 52.4 +/- 12.6 yrs, respectively; p < 0.005). The cumulative MTX dose ranged from 65 to 580 mg at the time pneumonitis developed. Five of the patients (83%) had preexisting interstitial abnormalities, while only 29 of the 278 patients without MTX pneumonitis (10%) had such abnormalities (p < 0.001). The frequency of adverse effects due to previous treatment with disease modifying antirheumatic drugs (DMARD) was 66.7% in MTX pneumonitis patients and 14.3% in the other 278 patients (p < 0.01). CONCLUSION: Advanced age, preexisting interstitial abnormalities, and previous adverse reactions to DMARD may be associated with MTX pneumonitis. Patients with these characteristics require careful monitoring during MTX therapy.     

Methotrexate treatment of ectopic pregnancy. A pilot study

The incidence of ectopic pregnancy is rising but the clinical presentation of the disease has changed simultaneously. Nowadays, the majority of ectopic pregnancies are diagnosed before rupture. This stimulated us to attempt methotrexate therapy (1 mg/kg body weight injected locally or 50 mg given orally) in 12 cases verified by transvaginal ultrasound and presenting with increasing beta-hCG values. The treatment proved successful in 67% of the cases, even though high levels of beta-hCG and foetal heart activity were accepted as inclusion criteria. Eight patients later achieved intrauterine pregnancies, and seven healthy babies were delivered. Randomized, controlled studies are needed.     

Trans-signaling by cytokine and growth factor receptors

OBJECTIVE: to compare methotrexate (MTX) to laparoscopic salpingotomy for conservative management of ectopic pregnancy (EP). DESIGN: prospective randomized study. PATIENTS: eighty-nine patients were randomized into 2 groups using a random number table. Inclusion criteria were an EP visualized by ultrasound with a pretherapeutic score < or = 13 as assessed by 6 criteria graded from 1 to 3: gestational age, hCG level, P level, abdominal pain, volume of the hemoperitoneum, and diameter of the hematosalpinx. INTERVENTIONS: 1 mg/kg of MTX injected transvaginally into the ectopic pregnancy without anaesthesia or IM administration (1.5 mg/kg) when EP cannot be safely or easily punctured (group 1) versus laparoscopic salpingotomy (group 2). RESULTS: the success rates defined by hCG levels returned to normal (< 10 mlU/mL) were 43 out of 46 in group 1 and 40 out of 43 in group 2. Medical treatment was significantly associated with shorter post-operative stay (24 vs 46 hours). hCG return to normal was quicker after laparoscopic treatment (13 vs 29 days). Reproductive performances were similar in both groups. CONCLUSIONS: in selected cases of EP with a pretherapeutic score < or = 13, MTX treatment appeared to be as safe and efficient as was conservative treatment by laparoscopy, an expectant management should be offered as a treatment option only in women fulfilling the criteria for a good prognostic.     

Chorionic gonadotropin and progesterone levels in ectopic pregnancy

It is assumed that one function of hCG is to preserve the developing corpus luteum and maintain pregnancy by producing progesterone and thus preventing menstrual shedding. In 8 of 17 cases of ectopic pregnancy, progesterone values were in the range of the proliferative phase of a normal cycle (0.1-1ng/ml), whereas the levels of hCG were 299-1600 mIU/ml. In 8 cases the progesterone levels were in the range of the secretory phase (2.3-6.9 ng/ml), and the hCG level was 182-5500 mIU/ml. In 1 case only was the progesterone level 15.0 ng/ml with an hCG level of 325 mIU/ml. In normal pregnancies of the same gestational age, the values of progesterone were 3.8-18.7 ng/ml, and the levels of hCG were 260-1300 mIU/ml. It seems that in addition to the level of hCG, a normal fetoplacental unit is needed for the preservation of the function of the corpus luteum.     

Analysis of 369 abortions conducted by mifepristone (RU486) associated with sulprostone in a French family planning center

OBJECTIVE: To investigate the use of oral mifepristone (RU486; Roussel-Uclaf, Paris, France) associated with IM injection of sulprostone (Schering, Lys-Lez-Lannoy, France) for the induction of legal abortion (7 weeks of amenorrhea in France). DESIGN: An uncontrolled observational study. SETTING: A public family planning center in Paris. PATIENTS: Three hundred sixty-nine (369) pregnant women with up to 7 weeks amenorrhea undergoing legal abortion. INTERVENTIONS: Six hundred milligrams (600 mg) of oral mifepristone followed 48 hours later by an IM injection of 250 micrograms of sulprostone. MAIN OUTCOME MEASURES: Frequency of complete abortion and the need for subsequent surgical evacuation, hospitalization, and blood transfusion. Measurement of the beta-hCG concentration before and 14 days after the oral administration of mifepristone. RESULTS: There was complete abortion in 93.2% of the cases. Of the 25 failures, 8 were continued pregnancies, 6 terminated pregnancy but without expulsion of the conceptus, and 11 were placenta retentions. Eight women required short hospitalization, but none needed blood transfusion. Among the 25 failures, 23 had a beta-hCG concentration > 500 IU/mL [sensitivity 92%, specificity 83%]. CONCLUSION: The sequential use of oral mifepristone and IM injection of sulprostone is effective in inducing abortion up to 7 weeks of amenorrhea. Nevertheless the risk of maternal morbidity associated with sulprostone and also the risk of fetal malformations in cases of continued pregnancy indicate that this method should only be used in specialist centers.     

Analysis of three hundred fifteen ectopic pregnancies treated with single-dose methotrexate

OBJECTIVES: The objective of this study was to review the largest single series of ectopic pregnancies treated with single-dose methotrexate reported to date. STUDY DESIGN: A review of 315 patients with unruptured ectopic pregnancies treated with single-dose methotrexate 50 mg/m2 from March 21, 1990, to March 1, 1997, was performed. RESULTS: Overall 287 patients were successfully treated with methotrexate for a success rate of 90.1%. Six patients electively withdrew and requested surgery within 1 week of starting therapy. Excluding withdrawals the overall success rate was 92.9%. Ten patients with an ectopic pregnancy > 3.5 cm but < or = 4 cm in size were treated for a 90% success rate. Forty-four patients with positive ectopic cardiac activity were treated with an 87.5% success rate. CONCLUSIONS: This large series indicates that single-dose intramuscular methotrexate for treatment of ectopic pregnancy is associated with an excellent overall success rate.     

Ectopic pregnancy: criteria to choose therapy

The ectopic pregnancy (EP) could be treated by spontaneous resolution, or medical treatment or laparoscopic treatment. Spontaneous resolution of EP with beta hCG < 1,000 mUl/ml, plasmatic progesterone < 5 ng/ml had 74% success rate. Methotrexate (MTX) injection is the common Medical treatment of EP with beta hCG < or = 5,000 mUl/ml and mean diameter of EP < or = 3 cm: a single dose of 50 mg/m2 or 1 mg/kg intramuscular injection had 93.4% success rate; local injection under sonographic control (1 mg/kg) had 80.2% success rate. The surgical conservative treatment by laparoscopy had 94% success rate.     

Induction of single ovulation by sequential follicle-stimulating hormone and pulsatile gonadotropin-releasing hormone treatment

OBJECTIVE: To induce single follicular ovulation by sequential treatment with FSH and pulsatile GnRH. DESIGN: Prospective study. PATIENTS: Eighteen hypogonadotropic anovulatory patients. INTERVENTIONS: In sequential treatment, daily FSH injection was switched to pulsatile GnRH administration (20 micrograms/120 minutes SC) when the follicle diameter reached 11 mm. In conventional FSH treatment, daily FSH injection was continued. In both cycles, hCG was given when the diameter of the dominant follicle reached 18 mm. MAIN OUTCOME MEASURES: Developed follicle numbers and serum FSH concentrations during treatment. RESULTS: Single follicular development was achieved in 80.0% of cycles by sequential treatment but in no cycle by conventional FSH treatment. The number of developed follicles was 1.26 +/- 0.55 (mean +/- SD) on sequential treatment and 3.94 +/- 1.48 on conventional FSH treatment. Preovulatory FSH level was significantly lower on sequential treatment than on conventional FSH treatment (5.26 +/- 1.80 versus 11.55 +/- 3.43 mIU/mL [conversion factor to SI unit, 1.00]). CONCLUSION: The sequential treatment achieved single follicular development without complications. The sequential FSH-pulsatile GnRH treatment may offer a better chance for development of a single dominant follicle and ovulation.     

Mycophenolatemofetil in ocular immunological disorders. A survey of the literature with 3 case reports

OBJECTIVE: The objective of this study was to prospectively evaluate the sperm migration test (SMT) as a discriminator in couples undergoing intrauterine insemination (IUI). PATIENTS AND METHODS: 261 couples underwent 797 IUI treatment cycles involving gonadotropin stimulation in the three year period. All had a diagnosis of unexplained infertility. All male partners underwent a repeat standard seminal analysis and SMT prior to the female partner undergoing controlled ovarian stimulation. RESULTS: Despite apparently normal seminal analyses before referral, in 22 samples the sperm concentration, motility or morphology were abnormal (WHO criteria). Of these, 20 couples underwent 109 cycles and achieved 2 pregnancies giving a pregnancy rate of 1.8% per cycle and a cumulative pregnancy rate of 10% per couple. From the remaining couples with normal seminal analyses, 71 had an SMT <5 million/mL and 168 had an SMT >5 million/mL. The suboptimal SMT group underwent 276 cycles (3.89 cycles per couple) and achieved 18 pregnancies giving a pregnancy rate of 6.5% per cycle and a cumulative pregnancy rate of 25.4%. The normal SMT group underwent 412 cycles (2.45 cycles per couple) and achieved 60 pregnancies giving a pregnancy rate of 14.6% per cycle and a cumulative pregnancy rate of 35.7%. CONCLUSIONS: We confirm that abnormal seminal analysis leads to poor pregnancy rates with IUI. However, an SMT <5 million/mL despite normal seminal analysis (WHO criteria) also leads to significantly worse pregnancy rates. We would recommend that prior to IUI, couples are screened using the SMT.     

Health sector reform: priorities and packages

Using time-resolved fluorometry, a simple one-step dual-label immunometric assay has been developed, which allows simultaneous determination of pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotrophin (beta-hCG) in first-trimester maternal serum samples. Two monoclonal antibodies were biotinylated and immobilized onto the surface of streptavidin-coated microtitration plates, and used to capture PAPP-A and beta-hCG. respectively. Europium (Eu) and Samarium (Sm) chelates were conjugated to two additional monoclonal antibodies acting as detection antibodies for PAPP-A and beta-hCG. The assay was performed using a 4-h one-step format. The within-run precision with buffer-based calibrators was below 8% over the working range of PAPP-A (40-10000 mIU/l) and beta-hCG (7.3-525 micrograms/l) and no hook effect was observed. The intra- and inter-assay coefficients of variation were below 7.1% for serum samples. PAPP-A and beta-hCG concentrations measured by the dual assay in 39 first-trimester serum samples correlated excellently with those obtained by DELFIA single-label PAPP-A (r = 0.997) and the beta-hCG part (r = 0.993) of the DELFIA AFP/beta hCG dual-label assay.     

Revascularization of internal iliac arteries during aortoiliac surgery: a multicenter study

Prenatal screening for fetal abnormalities in an accepted part of modern obstetric management. Improvements on current screening procedures need to address increased diagnostic efficacy and earlier diagnosis. This study evaluates diagnostic efficacy of PAPP-A and F beta-hCG in the detection of first trimester pregnancy abnormalities, including Down syndrome (DS). Of 731 pregnant volunteers, obtained from a mature age population undergoing chorionic villus sampling (CVS), 17 DS and 11 compromised (six numerical (excluding sex chromosome) aneuploidies, five spontaneously failed) pregnancies were detected. Application of an algorithm, which combines PAPP-A and F beta-hCG levels with material age, detected 66.6 per cent of DS pregnancies for a five per cent false positive rate. Similarly, for a 1-2 per cent recall rate, 72.2 per cent of compromised pregnancies were detected. This report supports the notion that prenatal screening at 9-12 weeks of pregnancy is achievable with PAPP-A and F beta hCG quantitation. Whereas mid-gestational screening targetted the detection of fetal abnormalities, screening earlier in pregnancy will detect other pregnancy-related abnormalities, in addition to aneuploidy.     

Selective salpingography and tubal cannulation through hysteroscopy

In this paper the procedure of selective salpingography and tubal cannulation through hysteroscopy for diagnosis and treatment of fallopian tube obstruction at the interstitial portion was introduced. We combined hysteroscopic tubal cannulation with selective salpingography under fluoroscopic quidance in 28 infertile women with 49 obstructed interstitial portion of fallopian tubes diagnosed previously. After the procedures 27 tubes (55.1%) became patent in 16 cases. In 16 women with patent tubes followed up over 6 months after the procedures 5 intrauterine pregnancies occurred. This procedure is a safe and simple diagnostic method to identify fallopian tube obstruction at the interstitial portion and may alos serve as a therapeutic approach in some of these patients.