Differential diagnosis of early human pregnancies: impact of different diagnostic measures.

A total of 261 women in early pregnancy, either with mild symptoms of ectopic pregnancy (EP) or being at an increased risk for this condition, were included in a longitudinal study. The effectiveness of different diagnostic measures in obtaining correct final diagnoses was analyzed. In addition to clinical findings and symptoms, the use of serum human chorionic gonadotropin, serum progesterone, endovaginal sonography and a risk score for EP were all proven to be valuable in distinguishing normal intrauterine pregnancies from pathological pregnancies.     

Local luteolytic effect of prostaglandin F2 alpha in the human corpus luteum.

OBJECTIVE: To evaluate the effects of prostaglandin (PG)F2 alpha on human corpus luteum (CL) function in vivo. DESIGN: The effects of a single injection of PGF2 alpha into the CL was studied. SETTING: The patients underwent elective surgery at the Department of Obstetrics and Gynecology, Sahlgrenska Hospital, University of G?teborg, Sweden. PARTICIPANTS: Twenty women with regular menstrual cycles undergoing laparoscopy for legal sterilization with tubal clips volunteered for the study. INTERVENTIONS: Prostaglandin F2 alpha (3 mg) was injected through the abdominal wall into the CL. In control cases, vehicle was injected into the CL or PGF2 alpha into the contralateral ovary. MAIN OUTCOME MEASURE: After the injections, serum was analyzed for progesterone (P) and luteinizing hormone using fluoroimmunoassay and enzyme-immunoassay, respectively. Menstrual data were recorded. RESULTS: In contrast to control cases, intraluteal injection of PGF2 alpha caused both an immediate fall of greater than 30% in serum P and a shortening of the luteal phase by 2 to 5 days. Luteinizing hormone varied independently of the changes in serum P levels. CONCLUSION: The results suggest a local role for PGF2 alpha in human luteolysis.     

Human granulosa cell tumor: stimulation of steroidogenesis by gonadotropins in vitro.

A 59-year-old previously oophorectomized woman underwent surgery for a recurrent malignant granulosa cell tumor. Specimens and dispersed cells from the tumor tissue were incubated for 2 hr and cultured for 48 hr, respectively, with and without gonadotropins. Steroids and cyclic AMP (cAMP) concentrations were measured in the incubation and culture media. Incubated specimens from the tumor tissue released measurable amounts of cAMP, progesterone, and estradiol into the medium. Human follicle-stimulating hormone (FSH) 1 microgram/ml significantly stimulated the formation of cAMP and both steroids. Human luteinizing hormone (LH) 1 microgram/ml stimulated cAMP and progesterone but not estradiol release. Human chorionic gonadotropin (hCG) 10 micrograms/ml stimulated cAMP and progesterone formation in tumor tissue but was totally devoid of effect on estradiol release. In the tissue culture experiments progesterone and estradiol were formed in considerable amounts, with a higher capacity for progesterone than for estradiol. Progesterone formation was stimulated by FSH and hCG, while estradiol release was stimulated only by hCG. The addition of testosterone significantly enhanced estradiol formation in both incubation and culture experiments. It is concluded that the steroidogenesis of this granulosa cell tumor is sensitive to gonadotropins.     

Pregnancy: Bereavement, grieving and psychological morbidity after first trimester spontaneous abortion: comparing expectant management with surgical evacuation

Early pregnancy loss is a profound adverse life event for manywomen, and increased psychiatric morbidity has been shown tooccur after spontaneous abortion. Dilatation and curettage (D&C)has been the cornerstone in the treatment of first trimesterspontaneous abortion over the last few decades. During recentyears the possibility of conservative management has, however,been increasingly discussed. In a prospective randomized trial,we compared psychological reactions and morbidity, after eitherexpect ant management or D&C, for miscarriages of <13weeks gestation In which a transvaginal ultrasound examinationshowed Intrauterine tissue and/or blood clots with an antero-posteriordiameter of between 15 and 50 mm. Of the 86 patients included,58 were randomized to expectant management and 28 to primaryD&C. In patients randomized to expectant management, pregnancyproducts shown by transvaginal ultrasound disappeared within3 days in 43 cases (74%), whereas 15 patients (26%) underwentD&C owing to retained products of conception after 3 days.At 2 weeks after indusion, all patients answered self-administeredquestionnaires, induding visual analogue scales, concerningtheir experience of the pregnancy loss, the present situationand concerns about the future. A brief anxiety status inventorywas included. This study showed no increase in anxiety or depressivereactions 2 weeks after a first trimester spontaneous abortionwhen these patients were compared with non-pregnant healthyworking females 19–39 years of age. Moreover, there wereno significant differences in psychological reactions betweenpatients managed either expectantly or by D&C.     

Characterization of a monoclonal antibody inhibiting the biological activity of human chorionic gonadotrophin

A mouse monoclonal antibody (MCA), raised against human chorionicgonadotrophin (HCG) and coded 130A, was characterized with severaltypes of immunoassay and with in-vitro and in-vivo bioassays.MCA 130A binds strongly to the intact HCG molecule but lessso to either -or -subunit; The dissociation constant of theMCA-HCG complex was found to be in the order of 70 pmol/l. MCA130A inhibits the biological activity of HCG very effectively,both in vitro and in vivo. In a competitive immunoassay MCA130A binds 30 x better to HCG than to human luteinizing hormone(HLH). The selectivity in the bioassays was much higher, e.g.in vitro, 50% inhibition of HLH-stimulated testosterone productionrequires 2600 x as much MCA as is needed for inhibiting HCG-stimulatedproduction. Possible reasons for this difference in selectivityare discussed     

Ultrasound studies of vascular and morphological changes in the human uterus after a positive self-test for the urinary luteinizing hormone surge

The aim of the study reported here was to establish complementarydata for changes in uterine size, echogenicity and vascularityduring the menstrual cycle relative to a positive self-testfor urinary luteinizing hormone (LH) and day 1 of next menses.Thirteen volunteers (aged 23-32 years) with apparently regularmenstrual cycles were recruited from the nursing staff. Theplan was to examine all women by transvaginal ultrasonographywith colour Doppler imaging on day 11 of the menstrual cycle.A urinary LH self-test was to be used daily until a positiveresult was obtained and the women were to be re-scanned dailyuntil the dominant follicle had ruptured. All women were thento be scanned at least every 48 h (within ±2 h of thesame time of day) until day 6 of the next menstrual cycle. Matchedsamples of peripheral blood were taken at the time of each scanfor hormone analysis. The main outcome measures were the timesof follicular rupture, a positive test result for urinary LHand the start of menses, uterine volume, cavity length, endometrialthickness and grade, pulsatility index (PI), and timeaveragedand peak systolic maximum velocities in uterine and radial arteriesand in subendometrial vessels. Nine women fulfilled the criteriafor an ovulatory cycle, and seven provided data over the completestudy. The principal changes relative to a positive urinaryLH test were (i) a continued rise in endometrial thickness todays 3 and 4 (this index then remained relatively constant,but the layered appearance was lost) and (ii) a gradual decreasein the uterine arterial PI. There was a significant rise inuterine volume, cavity length and uterine arterial PI aroundthe time of the next menses, and a fall in endometrial thicknessand blood velocity in the uterine and radial arteries and subendometrialvessels. The data may have implications for the assessment ofreproductive status and the design of future studies on disordersof implantation or menstruation.     

Adhesion formation after laparoscopic surgery in tubal pregnancy: a randomized trial versus laparotomy.

OBJECTIVE: Women with ectopic pregnancy (EP) who have been operated on by laparoscopy are thought to have improved subsequent fertility, probably because of less adhesion formation. We aimed to evaluate the adhesion formation after laparoscopy as compared with laparotomy in a randomized trial. DESIGN: One hundred five patients with tubal pregnancy were stratified with regard to age and risk factors and randomized to surgery by laparoscopy or laparotomy. To evaluate adhesion formation and tubal status, 73 patients with strong desire of pregnancy underwent a second-look laparoscopy. The adhesion status at the ipsilateral and contralateral side at primary surgery was compared with the status at second-look laparoscopy. RESULTS: Patients operated on by laparotomy developed significantly more adhesions at the operated side than patients operated on by laparoscopy (P less than 0.001). Substantially more patients in the laparotomy group underwent adhesiolysis at second-look laparoscopy than did patients in the laparoscopy group. Tubal patency did not differ between the groups. CONCLUSIONS: Laparoscopic treatment of EP results in less impairment of the pelvic status compared with conventional conservative surgery.     

Ovary and ovulation: Interaction between oxytocin and prostaglandin F2{alpha} in human corpus luteum?

The effect of a single injection of oxytocin into the corpusluteum, with or without pretreatment with a prostaglandin synthetaseinhibitor, was studied in order to investigate possible localinteractions between prostaglandin (PG)F₂ and oxytocin in theregulation of the human corpus luteum. Oxytocin (4 IU) was injectedthrough the abdominal wall into the corpus luteum in women undergoinglaparoscopy for legal sterilization. In the control cases, salinewas injected into the corpus luteum, or oxytocin was injectedinto the contralateral ovary. Oxytocin injected into the corpusluteum caused a fall in serum progesterone and shortened theluteal phase. These effects were not seen following injectionof saline into the corpus luteum, or following injection ofoxytocin into the contralateral ovary. After the injection ofoxytocin into the corpus luteum a rise in 15-keto-dihydro-PGF₂,a PGF₂ metabolite, was seen. The changes in serum progesteronecaused by injection of oxytocin into the corpus luteum couldbe prevented if a PG synthetase inhibitor was given before theinjection. These findings suggest that local interaction betweenoxytocin and PGF₂ plays a role in the regulation of the humancorpus luteum.     

Pregnancy: Prediction of persistent trophoblastic activity after local prostaglandin F2{alpha} injection for ectopic pregnancy

A total of 60 patients underwent injection of prostaglandin(PG)F₂ into the affected tube and corpus luteum. Two serum samples,with a mean interval of 2.1 days, were taken pre-operativelyand human chorionic gonadotrophin (HCG) and progesterone weredetermined by fluoroimmunoassay retrospectively. Cases requiringa second intervention (n = 8) were compared with uncomplicatedcases (n = 52). The receiver-operator characteristic curve wasused to determine optimal discriminatory levels of each diagnostictest. Among the complicated cases, 75% had progesterone values> 20 nmol/l and 100% had a daily HCG increase > 50 IU/l.The corresponding figures for the uncomplicated cases were 17%and 23% respectively. A ‘high-risk’ group representing12% of the patient material was identified, and was biochemicallyprofiled by serum progesterone values > 20 nmol/l, togetherwith daily HCG changes >+50 IU/l/day. These patients hadan 86% risk for a second intervention. Conversely, 88% of patientshad only a 4% risk for such an intervention. We conclude thatthe combined use of two sequential serum HCG samples and oneserum progesterone sample, the last of each taken not more than24 h pre-operatively, can predict the risk for a complicatedcourse following local injection of 15-methyI-PGF₂ for smalltubal pregnancies.     

Evidence for nitric oxide acting as a luteolytic factor in the human corpus luteum

The aims of the present study were to characterize the expression and cellular localization of isoforms of nitric oxide synthase (NOS) in the human corpus luteum (CL) and to determine the effects of nitric oxide (NO) on CL steroidogenesis. Immunoblotting analyses revealed that endothelial NOS (eNOS) is the most abundant isoform in human CL with highest values during the late luteal phase. Immunoreactive eNOS was localized predominantely in the theca lutein layer, being particularly abundant in endothelial cells, but with positive staining also in some steroidogenic cells. Immunoreactive inducible NOS (iNOS) was also detected, but to lesser degree, and did not display apparent phase-specific changes. The effect of NO on CL steroid synthesis was examined using human chorionic gonadotrophin (HCG)-stimulated dispersed CL cells cultured in vitro. Progesterone production was significantly decreased (P < 0.05) by the NO donor spermine NONOate (10(-5) mol/l) in cells of the late, but not mid-, luteal phase. To investigate a potential link between NO and the local prostaglandins (PG), concentrations of PGF(2alpha) and PGE(2) were measured in culture medium. NO significantly increased (P < 0.05) concentrations of both PGF(2alpha) and PGE(2) during the late luteal phase. It is concluded that NO may be luteolytic in the human CL of menstruation.