Is luteal function maintained by factors other than chorionic gonadotrophin in early pregnancy?

Women with ectopic pregnancy (n = 14) and early embryonic arrest(‘blighted ovum’) (n = 9) were studied 16 days afterconception, at a time when they were asymptomatic and serumconcentrations of -human chorionic gonadotrophin (HCG) werein the normal range and increasing at an apparently normal rate.Serum progesterone and oestradiol concentrations were comparedwith those from normal women matched for gestational age andserum -HCG concentration whose singleton intra-uterine pregnanciesproceeded normally beyond 20 weeks. Mean serum progesteroneconcentrations were significantly lower in the women with ectopicpregnancies than in matched controls (P < 0.002); however,there was no difference in the serum progesterone concentrationsbetween women with blighted ova and matched controls. Statisticallysignificant differences were not seen in serum oestradiol concentrationsbetween either group and matched controls. Similarly there wasno difference in serum progesterone or oestradiol concentrationsin 20 women who conceived ectopic pregnancies and 20 women conceivingblighted ovum pregnancies and their matched intra-uterine controlswhen conception followed ovarian stimulation. The low serumprogesterone concentrations seen in ectopic pregnancy suggestthat there is a specific and selective deficiency in progesteronesynthesis, which implies that factors other than HCG may influenceluteal function.     

Pregnancy: Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older

We analysed the results of oocyte donation to women of advancedreproductive age (45 years old) and followed their pregnanciesthrough to delivery in order to assess obstetrical outcomes.Patients (n = 162) aged 45–59 years (mean ± SD;47.3 ± 3.4 years) underwent 218 consecutive attemptsto achieve pregnancy. Oocytes (16.2 ± 7.2 per retrieval)were provided by donors 35 years old. Cleaving embryos (8.2± 4.8 zygotes/couple) were transferred trans-cervically(4.5 ± 1.1 per embryo transfer) to recipients prescribedoral micronized oestradiol and intramuscular progesterone. Followingoocyte aspiration there were six instances of non-fertilization(2.8%) and 212 embryo transfers. A total of 103 pregnancieswas established for an overall pregnancy rate (PR) of 48.6%,which included 17 preclinical pregnancies, 12 spontaneous abortions,and 74 delivered pregnancies (clinical PR 40.6%; delivered PR34.9%). Multiple gestations were frequent (n = 29; 39.2% ofpregnancies) and included 20 twins, seven triplets, and twoquadruplets. Two of the triplet and both of the quadruplet pregnanciesunderwent selective reduction to twins. Antenatal complicationsoccurred in 28 women (37.8% of deliveries) and included pretermlabour (n = 9), gestational hypertension (n = 8), gestationaldiabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia(n = 2), HELLP syndrome (n = 2), and fetal growth retardation(n = 2). 48 (64.8%) deliveries were by Caesa-rean section. Thegestational age at delivery for singletons was 383 ±1.3 weeks (range 35–41 weeks), with birth weight 3218± 513 g (range 1870–4775 g); twins 35.9 ±2.0 weeks (range 32–39 weeks), birth weight 2558 ±497 g (range 1700-3450 g); and triplets 33.5 ± 0.7 weeks(range 32-34 weeks), birth weight 1775 ± 190 g (range1550-2100 g). Neonatal complications (4.6% of babies born) includedgrowth retardation (n = 2), trisomy 21 (n = 1), ventricularseptal defect (n = 1), and small bowel obstruction (n = 1).There were no maternal or neonatal deaths. We conclude thatoocyte donation to women of advanced reproductive age is highlysuccessful in establishing pregnancy. However, despite carefulantenatal screening, obstetrical complications are common, oftensecondary to multiple gestation.     

Predictive value of human chorionic gonadotrophin in the outcome of early pregnancy after in-vitro fertilization and spontaneous conception

This prospective study analyses the value of the -subunit ofhuman chorionic gonadotrophin (-HCG) in 120 pregnancies obtainedafter in-vitro fertilization (IVF)-embryo transfer. Spontaneousconception cycles (n = 16) were also analysed allowing a comparisonbetween these two forms of conception. Of the 120 clinical pregnancies,48 started as single gestations and 50 started with two or moresacs. There were 14 clinical abortions and eight ectopic pregnancies.All subjects had blood samples taken under a fixed protocolon days 11, 14, 17, 20 and 23 after follicular aspiration. Weeklysamples were obtained thereafter until day 60 from ovum retrieval.Transvaginal ultrasounds were performed at weekly intervals,starting on day 23 after follicular aspiration. In spontaneousconception cycles blood samples were obtained daily, startingon the day of follicular rupture. In spontaneous conceptioncycles and in IVF– embryo transfer conceptions, the doublingtime (DT) of ;-HCG was 1.4 ± 0.3 and 1.6 ± 0.4days respectively. This difference was not significant. In multigesta–tions,the DT was 1.5 ± 0.3 days. The absolute values of -HCGin early spontaneous gestations were significantly higher thanin IVF—embryo transfer cycles, suggesting that the blastocystimplants with less cellular mass when initiated in vitro ascompared with the in-vivo condition. The early prediction ofectopic pregnancy and spontaneous clinical abortion was analysedby the -HCG profile as well as the absolute values in comparisonto normal pregnancies. Both parameters showed significant differencesas early as the interval between days 11 and 23 from follicularaspiration. This study provides a comprehensive approach tothe evaluation of the outcome of early gestation in terms ofthe predictability of single and multigestation, ectopic pregnancyand early abortion.     

The role of a single free {beta}-human chorionic gonadotrophin measurement in the diagnosis of early pregnancy failure and the prognosis of fetal viability

This prospective controlled study investigated the concentrationsof free -human chorionic gonadotrophin (HCG) subunit in 554women with a singleton intrauterine or tubal pregnancy. Theypresented with vaginal bleeding and/or abdominal pain in thefirst 18 weeks of pregnancy. The control group comprised 156women with musculo-skeletal pain and no vaginal bleeding. Theirpregnancies continued to term. The study group comprised 398women (141 threatened-continuing pregnancies, 37 threatened-miscarriages,185 non-continuing pregnancies and 35 tubal pregnancies). Free-HCG concentrations were significantly lower in the non-continuing,threatened-miscarriage and tubal pregnancy groups [mean 4.62,6.50 and 4.27 ng/ml respectively; 95% confidence interval (CI)3.75–-5.69, 4.46–9.48 and 2.92–6.2 respectively]than in the control and threatened-continuing groups (mean 41.61and 48.22 ng/ml respectively; 95% CI 34.53–50.13 and 42.03–55.32respectively) (P < 0.001 in all cases). A cut-off value at20 ng/ml was found to differentiate between the ‘viable’(control and threatened-continuing) and the ‘abnormal’(non-continuing, threatened-miscarriage and tubal) pregnancies,with 88.3% sensitivity and 82.6% positive predictive value.An excellent diagnostic and prognostic usability of free HCGwas confirmed by a receiver operating characteristic curve plotIn conclusion, a single serum free -HCG measurement taken inearly pregnancy is valuable in the immediate diagnosis of earlypregnancy failure and the long-term prognosis of viability.     

Pregnancy: Proliferative activity in ectopic trophoblastic tissue

Clinical observations have shown that tubal pregnancies developindividually different biological activities such as differentgrowth rates, levels of beta human chorionic gonadotrophin (-HCG),or rates of tubal wall destruction. In the present study, weevaluated the proliferative activity of ectopic cytotrophoblastictissue using immunocytochemistry with antibodies to Ki-67 (cloneMIB-1). The rates of proliferation obtained were related tothe maternal serum -HCG values. Reference data were obtainedfrom placentas of intact intrauterine pregnancies c(group I,n = 14). The proliferative activity of this tissue was comparedto that of cytotrophoblastic tissue of tubal pregnancies (groupII, n = 27). Ki-67-immunostained as well as non-stained cytotrophoblasticnuclei of the villi and the trophoblastic columns were countedseparately, and results were expressed as percentage of positivecells. Serum -HCG values were determined twice, 48 h and immediatelybefore operation. The cytotrophoblastic cells of intact intrauterinepregnancies (group I) showed uniform and high proliferativeactivities (80% on average in villi, 84% on average in columns).The average Ki-67 proliferation rate was significantly lower(P < 0.001) in trophoblastic tissue of tubal pregnancies(group II; 42% on average in villi, 61% on average in columns).Within the group of tubal pregnancies, higher intragroup differenceswere observed. The number of Ki-67-labelled cells was independentof the absolute preoperative serum -HCG values in both groups,yet they were clearly related to the relative increase of P-HCGin maternal serum. At higher proliferation rates, there wasa significant, growing increase of -HCG values (P < 0.01).We have found immunohistochemical evidence to support the previousclinical speculations that tubal pregnancies develop more heterogeneouslyand more slowly than intact intrauterine pregnancies. The developmentof the -HCG concentrations may be taken as an indirect parameter,reflecting proliferative activity of the trophoblast.     

Association of early {beta}-human chorionic gonadotrophin values with pregnancy wastage and multiple implantation in a donor oocyte programme

An early marker predictive of a viable pregnancy would easethe anxiety associated with positive pregnancy tests after theuse of donor oocytes. We examined the predictive value of anearly serum quantitative human chorionic gonadotrophin (Q-HCG)concentration on pregnancy outcome following oocyte donation.Embryo transfers after oocyte donation resulting in a positiveserum -HCG were examined beginning 9 days after embryo transferfrom those samples assayed in our laboratory (n = 77). Q-HCGconcentrations were measured in our laboratory by an immunoradiometricassay utilizing the first International Reference Preparation.Implantations were defined as the number of gestational sacsvisualized by transvaginal ultrasound 21 days after embryo transfer.Biochemical pregnancies were those with transient elevationsin -HCG concentration but without implantation sites. Spontaneousabortions were characterized by an implantation site with theeventual arrest of development. Ongoing/delivered pregnanciesdeveloped appropriately and proceeded beyond the first trimester.Day 9 Q-HCG concentrations did not differentiate between biochemicalpregnancies/spontaneous abortions and ongoing/delivered pregnancies,although mean ± SD concentrations for biochemical pregnancieswere significantly lower than those for the other groups (P< 0.0001): biochemical pregnancies, n = 18, 5.8 ±8.9 mlU/ml, range 0–35; spontaneous abortions, n = 2,46.0 ± 10.0 mlU/ml, range 39–53; ongoing/deliveredpregnancies, n = 57, 41.5 ± 35.4 mlU/ml, range 0–214.In addition, day 9 Q-HCG concentrations did not differentiatebetween multiple implantations, although the implantation offour sacs had a significantly higher mean Q-HCG concentrationcompared with the implantation of fewer sacs (P > 0.0001):one sac, n = 22, 32.2 ± 21.5 mlU/ml, range 3–78;two sacs, n = 25, 35.8 ± 21.3, range 0–81; threesacs, n = 7, 47.1 ± 37.1 mlU/ml, range 22–126;four sacs, n = 4, 122.3 ± 62.4 mlU/ml, range 76–214.The positive predictive value of a Q-HCG >10 mlU/ml was 0.91(sensitivity 91%, specificity 75%). These initial data suggestthat early day 9 serum Q-HCG determinations do not accuratelyidentify viable pregnancies or multiple implantations. Evenan early negative pregnancy test should be repeated becauseit can be associated with a normal pregnancy.     

Rapid diagnosis of early ectopic pregnancy in an emergency gynaecology service--are measurements of progesterone, intact and free {beta} human chorionic gonadotrophin helpful?

The clinical usefulness of measuring serum concentrations ofprogesterone, human chorionic gonadotrophin (HCG) and the free-subunit of HCG in distinguishing between early viable and non-viablepregnancy, before an accurate ultrasound diagnosis is possible,was evaluated in a prospective study of patients presentingto our emergency gynaecology service with a clinical suspicionof ectopic pregnancy. Patients were selected on the basis ofinitial HCG concentrations; samples with HCG 25–10 000IU/I were later analysed for progesterone and free HCG. Of the181 patients studied, 38 (21%) had an ectopic pregnancy, 108(60%) had a spontaneous abortion and 35 (19%) had a viable intra-uterinepregnancy. Concentrations of HCG and free HCG in the group withviable pregnancies were significantly higher than in the groupwith ectopic pregnancy (P < 0.001) and than those destinedto miscarry (P < 0.01). Progesterone concentrations werealso significantly higher in the viable versus the ectopic andthe spontaneous abortion groups (P < 0.001 in each case).Despite these highly significant differences there was a degreeof overlap such that it was impossible to devise a cut-off levelfor any hormone analysed, either singly or in combination, whichwould offer a clinically useful predictor of outcome.     

Implantation: Impact of trophoblast penetration through the basal membrane on the efficacy of drug therapy in tubal pregnancies

Concentrations of -human chorionic gonadotrophin (HCG) of 2500IU/l are generally considered to be maximal for successful drugtherapy of tubal pregnancies [instillation of prostaglandin-F₂(PGF₂) or hyperosmolar glucose]. The purpose of our study wasto ascertain if there was an association between the significantlyhigher failure rates above this threshold value and the histologicallydetermined anatomopathological substratum. We therefore evaluatedthe impact of trophoblast penetration through the basal membraneof the Fallopian tube on the efficacy of drug therapy. Pre-operativeserum -HCG concentrations were compared with the histologicallydetermined trophoblast penetration, distinguishing between ectopicpregnancies with intra-luminal growths up to the myosalpinx,and those with extra-luminal growths going beyond the basalmembrane and penetrating the myosalpinx. Basic data were obtainedfrom a group of patients who received primary surgical treatmentbut it had never been the intention for them to receive drugtherapy (independently of their initial -HCG values; group I,n = 43). These reference data were compared with the findingsin preparations from another group of patients obtained duringsecondary surgical intervention, performed to achieve finalcure of tubal pregnancy after failure of primary PGF₂ instillation(group II, n = 30). Group I patients showed a significantlyhigher rate of intra-luminal trophoblast growths (P = 0.0001)at -HCG values <2500 IU/l; above this threshold value, extra-luminalspread was found significantly more often (P = 0.0001). In histologicalpreparations from group II, however, the number of extra-luminalgrowths was significantly higher even at low -HCG values (P= 0.007); at values above the threshold level, the distributionsin the two groups were similar. These results suggest that drugtherapy of tubal pregnancy becomes inefficient in tubal pregnanciesas soon as the trophoblast penetrates the basal membrane ofthe Fallopian tube.     

Endocrinology: The addition of a glucocorticoid to the protocol of programmed oocyte retrieval for in-vitro fertilization--a randomized study

A group of 78 infertile women, diagnosed as having tubal factorinfertility only, was enrolled in a prospective, randomizedstudy conducted to determine whether the addition of differentdoses of glucocorticoids to the protocol of ovulation inductionfor in-vitro fertilization (IVF) would be beneficial. Oocytenumbers, percentage of fertilization, oestradiol, luteinizinghormone and follicle stimulating hormone serum concentrations,number of embryo transfers and pregnancy rate were evaluated.Compared to control cycles (group A; n=24), the addition of0.5 mg (group B; n=27) or 1 mg dexamethasone (group C; n=27),combined with the protocol of programmed oocyte retrieval forIVF patients in the study, demonstrated equivalent results.The mean numbers of oocytes retrieved were 10.8±3.9 inthe control group, compared to 11.2±4.0 in group B and10.5±3.6 in group C. The fertilization rates were 69±21,66±18 and 70±15% respectively. The pregnancy rateswere 20, 16 and 20.8% respectively. The addition of up to 1mg dexamethasone daily to the protocol of ovulation inductionfor oocyte retrieval did not improve the overall IVF-embryotransfer outcome in patients with tubal factor infertility.     

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.     

Pregnancy: The influence of the number of embryos transferred in 1060 in-vitro fertilization pregnancies on miscarriage rates and pregnancy outcome

To assess the incidence of miscarriage, multiple pregnancy andoutcome of pregnancy in relation to the number of embryos transferredduring in-vitro fertilization (IVF), an analysis was performedof 1060 pregnancies conceived in a tertiary-referral IVF clinic.There was no difference in the miscarriage rate after transferof one or two embryos (37.7% and 34.6%), or after three or fourembryos (22.5% and 25.2%). The miscarriage rate was, however,higher when one or two embryos were transferred compared withthree (P < 0.01) or four embryos (P < 0.02). Of the 724ongoing pregnancies, 524 (72.3%) were singleton, 164 (22.7%)twin, 33 (4.6%) triplet and three (0.4%) quadruplet. The mean(±SD) ages of women with singleton, twin, triplet andquadruplet pregnancies were 32.5 (±3.8), 32.0 (±3.5),29.76 (±4.3) and 29.67 (±2.5) years respectively.The mean age of women with singleton and twin pregnancies wassimilar and both were greater than that of triplet pregnancies(P < 0.007). The overall perinatal mortality rate (PNMR)was 39.7/1000. The PNMR for singletons was 17.2/1000, for twins80.0/1000 and for triplets 30.6/1000. All of the babies fromthe three quadruplet pregnancies survived. There were more babieslost in the twin pregnancies than any other group, althoughthis only reached significance for singletons versus twins (P< 0.00005). We conclude that the incidence of miscarriageis increased in women in whom one or two embryos are transferred.Multiple pregnancies are more likely to occur in younger womenand are associated with a significantly higher rate of perinatalmortality.     

Pregnancy: Testosterone and androstenedione in premature ovarian failure pregnancies: evidence for an ovarian source of androgens in early pregnancy

Numerous anecdotal reports but few scientific approaches havesuggested an increase in androgens in early pregnancy. In thisstudy we have compared the concentration of serum androgens,testosterone and androstenedione in early pregnancy, startingwithin the cycle of conception. We have taken the opportunityto study women with premature ovarian failure where pregnancydevelops in the virtual absence of ovarian functions. This studydemonstrates that the concentration of testosterone (0.29 ±0.04 ng/ml) and androstenedione (1.770 ± 0.136 ng/ml)in these subjects is as low as, if not lower than, non-pregnantwomen (0.39 ± 0.02 and 2.170 ± 0.025 ng/ml), significantlyincreased in normal pregnancies (1.190 ± 0.118 and 3.920± 0.297 ng/ml; P < 0.05) and even further increasedin human menopausal gonadotrophin-treated cycles (1.990 ±0.230 and 8.19 ± 0.72 ng/ml; P < 0.05). These studiesdemonstrate that the ovary is a contributor to the circulatingconcentrations of testosterone and androstenedione startingwithin the cycle of conception.     

Diagnosing and preventing inherited disease: Detection of sickle gene by coelocentesis in early pregnancy: a new approach to prenatal diagnosis of single gene disorders

Coelomic fluid, placental tissue and maternal blood were collectedat 7–10 weeks gestation from each of 58 women undergoingelective termination of pregnancy for psychological indications.In all samples, a 364 bp fragment of the human -globin genespanning positions –23 to 341 was amplified. The restrictionendonuclease Ddel was used to detect the sickle mutation whichabolishes its restriction site. -Globin DNA was successfullyamplified from all samples. In 53 cases a normal maternal -globingenotype was detected. In three out of five cases, where thematernal haemoglobin phenotype was HbAS, heterozygosity forthe sickle mutation was demonstrated on analysis of coelomicfluid. In the remaining two cases a normal -globin genotypewas observed. Three further coelomic fluid samples were foundto be heterozygous for the sickle mutation. In these instancesthe maternal haemoglobin phenotype was normal, indicating paternaltransmission of the sickle gene. The results of the presentstudy have established that the diagnosis of sickle cell anaemia,and potentially other human single gene disorders, is feasibleby coelocentesis.     

Pregnancy: The expectant management of early pregnancies of uncertain site

The role of expectant management was evaluated in 80 women inwhom clinical examination, including vaginal ultrasound, hadfailed to identify the location of an early pregnancy. In 45cases, spontaneous resolution of the pregnancy products occurred.A normal intra-uterine pregnancy was diagnosed in 12 patients.A total of 23 patients underwent active therapeutic measuresdue to an ectopic pregnancy (n = 16) or a spontaneous abortion(n = 7). The effectiveness of different diagnostic measuresto identify patients suitable for expectant management was analysed.In 33/34 patients (97%) with a relative daily human chorionicgonadotrophin (HCG) change of <–5%, and a serum progesteroneconcentration of <20 nmol/l, spontaneous resolution of thepregnancy products occurred. Among 46 cases, with a relativedaily HCG change of >–5% and/or serum progesterone>20 nmol/l, active therapeutic measures were carried outin 22 cases (48%), a normal intra-uterine pregnancy was diagnosedin 12 cases (26%) and spontaneous resolution of the pregnancyproducts occurred in 12 cases (26%). In conclusion, the combinationof a single progesterone assay and serial HCG determinationsretrospectively identified early pregnancies of uncertain locationin whom expectant management was a safe management option.     

Immunology: Mitogen-induced lymphocyte proliferation and peripheral blood mononuclear cell {beta}-endorphin concentrations in primary dysmenorrhoea

Dysmenorrhoea is a recurrent painful disease which causes physicaland psychological stress. The purpose of the present study wasto investigate whether there was a measurable derangement ofimmune cells and immune responses in women with severe primarydysmenorrhoea. On day 26 of one cycle and on days 1 and 3 ofthe following cycle we measured polyclonal, mitogen-inducedlymphocyte proliferation and -endorphin concentration in peripheralblood mononuclear cells obtained from 16 infertile women withnormal pelvis, of whom eight had and eight did not have thedisorder. In women with dysmenorrhoea, polyclonal mitogen-inducedlymphocyte proliferation was lower than in controls on all 3days considered, but the difference was statistically significantonly on day 26 (43 605 ± 9876 µg/ml versus 67 305± 15 249 µg/ml; P < 0.01). Monocyte -endorphinconcentrations in the patients with dysmenorrhoea were significantlyelevated on day 3 compared to controls (67.8 ± 24.3 pg/10⁶cells versus 29.7 ± 6.9 pg/10⁶ cells; P < 0.05). Ourresults demonstrate that immune responses are modified in patientswith primary dysmenorrhoea. These effects are independent ofcirculating hormone concentrations and are consistent with therole of dysmenorrhoea as a stressful event.     

Pregnancy: Temporal relationship between the human chorionic gonadotrophin peak and the establishment of intervillous blood flow in early pregnancy

The purpose of this study was to investigate the temporal relationshipbetween the early pregnancy peak of circulating human chorionicgonadotrophin (HCG) concentration and the establishment of maternalblood flow in the placental intervillous space. The presenceof blood flow echoes within intervillous space was determinedby colour Doppler imaging from 44 women with clinically uncomplicatedpregnancy between 6 and 18 weeks gestation. Circulating HCG,free - and HCG subunits, oestradiol and progesterone concentrationswere immunoassayed in blood samples collected at the time ofDoppler examination. A continuous intervillous blood flow wasdetected in all cases with a gestational age 11.7 weeks (n =18) but never before this time. Circulating concentrations offree HCG, oestradiol and progesterone were linearly or exponentiallycorrelated with gestational age (r = 0.860, 0.903 and 0.538respectively, all with P < 0.001), indicating steady increaseof these hormones with advancing gestation. However, the bestfitted lines were found to be parabolic for HCG (r = 0.771,P < 0.001) and HCG (r = 0.695, P < 0.001), their highestpoints corresponding to 11.24 and 10.74 weeks gestational agerespectively. The close temporal relationship between the Doppleradvent of intervillous maternal blood flow and the HCG peaksuggests that the establishment of the intervillous blood flowis associated with the decline in circulating HCG concentrations.     

Identification of hormonal parameters for successful systemic single-dose methotrexate therapy in ectopic pregnancy

Single-dose methotrexate is an alternative to surgery in treatingectopic pregnancy. Because success rates vary, we sought toidentify factors which predict treatment outcome. A total of44 women with ectopic gestation were treated. The non-laparoscopicdiagnosis of ectopic pregnancy was made following history, physicalexamination, ultrasound, endometrial biopsy and the measurementof serial (-human chorionic gonadotrophin (HCG) and progesteroneconcentrations. Methotrexate (50 mg/m² i.m.) was administered,with a second dose given 1 week later in patients with plateauingor rising -HCG concentrations. Of 44 patients, 23 (52.3%) weresuccessfully treated with one dose. An additional 10 women (22.7%)were also successfully managed but required a second dose, givingan overall success rate of 75.0%. In all, 11 women (25.0%) requiredsurgery, four of whom experienced tubal rupture. Receiver operatorcurves were constructed to optimally select pretreatment -HCGand progesterone cut-off concentrations for successful treatment.Using -HCG <1500 IU/1 or progesterone <7.0 ng/ml (22.3nmol/1) as acut-off concentration produced a diagnostic testwith a sensitivity of 87.5%, a specificity of 90.0%, a positivepredictive value of 96.6% and a negative predictive value of69.2%. Conversely, this model predicts that patients with serum-HCG concentrations >1500 IU/1 and progesterone concentrations>7.0 ng/ml are at far greater risk of failing single-dosemethotrexate therapy.     

Maternal serum concentrations of pregnancy associated placental protein A and pregnancy specific {beta}-1-glycoprotein in multifetal pregnancies before and after fetal reduction

Placental function in multifetal pregnancies before and afterembryo reduction was investigated by measuring maternal serumconcentrations of pregnancy associated placental protein-A (PAPP-A)and pregnancy specific -1-glycoprotein (SP-1). Three groupsof pregnant women were studied following assisted reproduction;groups 1 and 2, were 12 singleton and 12 twin pregnancies respectively,and group 3 comprised 12 women with multifetal pregnancies undergoingembryo reduction. PAPP-A and SP-1 were measured serially at8–21 weeks gestation. In all pregnancies, maternal serumPAPP-A and SP-1 increased with gestation. In twin pregnanciesthe mean concentrations of SP-1 were significantly higher thanin singletons at all gestations, whereas for PAPP-A, concentrationswere similar between these groups. In multifetal pregnanciesbefore embryo reduction, the serum concentrations of both proteinswere significantly higher than in twin pregnancies. Followingreduction, the concentrations of PAPP-A remained significantlyhigher than for twins throughout, whereas the concentrationsof SP-1 gradually converged towards those of twins; by 19 weeksthere was no difference between the means of the two groups.These findings suggest that circulating concentrations of SP-1reflect total placenta mass, which is proportional to the numberof live fetuses, whereas the pattern of PAPP-A changes suggeststhat this protein is produced by the placenta, decidua and othertissues.     

Endocrinology: Ovarian hyperstimulation syndrome: pre-ovulatory serum concentrations of interleukin-6, interleukin-1 receptor antagonist and tumour necrosis factor-{alpha} cannot predict its occurrence

The pathogenesis of the ovarian hyperstimulation syndrome (OHSS)is poorly understood. Since significant elevations in cytokinesare found in 01155, our objective was to conduct a prospectivecase-controlled study to assess if preovulatory cytokine serumconcentrations can predict its occurrence. The study group wasselected from in-vitro fertilization patients who subsequentlydeveloped severe OHSS, along with a matched group who did notdevelop this complication (n = 20), and a healthy normal controlgroup (n = 10). Interleukin-6 (IL-6), interleukin-1 receptorantagonist (IL-1RA) and tumour necrosis factor- (TNF) measurementswere performed with sensitive immune-assays and confirmed withbioassays. Serum IL-6 (mean concentration ± SEM: 4.38± 0.36 pg/ml), IL-1RA (829 ± 292 pg/ml) and TNF(15.5 ± 132 pg/ml) concentrations did not show differencesthroughout the normal menstrual cycle group. Cytokine variabilityand pre-ovulatory values were similar in OHSS compared to controlledovarian hyperstiinulation (COH) patients. However, average follicularphase serum 1L-6 concentrations were higher in OHSS (8.71 ±0.41 pg/ml) and COH (7.66 ± 0.38 pg/ml) patients thanin normally menstruating women (4.34 ± 0.99 pg/ml) (P< 0.0001). Pre-ovulatory serum 1L-6 concentrations were alsohigher in OHSS (9 ± 0.94 pg/ml) and COH (73 ±0.97 pg/ml) patients than in controls (4.57 ± 1.1 pg/ml)(P < 0.01 and P < 0.04 respectively). IL-1RA and TNF concentrationswere comparable in all the groups. This study suggests thatcytokine measurements cannot be used to predict the occurrenceof OHSS prior to the administration of human chorionic gonadotrophin.     

The value of hysteroscopic evaluation in patients with preclinical in-vitro fertilization abortions

The study was conducted on 144 women who experienced preclinicalabortions, i.e. a transitory rise in -human chorionic gonadotrophin(HCG) without any clinical or sonographic evidence of pregnancy,to identify the relationship between preclinical abortions andintrauterine pathology. Hysteroscopy was performed 1–2weeks after the decline of -HCG concentrations to negative values.Intrauterine adhesions were detected in three patients (2.1%),most of these being of the mild type. Concomitant intrauterineabnormalities, mainly uterine septa, were found in 14 (9.7%)cases. We believe that preclinical abortions do not predisposeintrauterine adhesions and curettage is superfluous. An incompleteuterine septum seems to be the major factor predisposing thisearly pregnancy wastage. Hysteroscopy following this conditionis an easy and efficient means for both identifying intrauterinepathology and excluding adhesions.