Serum ske razine Anti-Müllerova hormona u žena s redovitim menstruacijskim ciklusom

Antimüllerian hormone (AMH ) is produced by Sertolli cells of the testes and granulosa cells of the ovaries. Recent studies have indicated that AMH may be a novel measure of ovarian reserve. Also, earlier reports have presented minimal fluctuations of AMH levels throughout the menstrual cycle. The aim of this preliminary study was to demonstrate the relation of serum AMH levels and age in women with regular menstrual cycles and normal hormonal regulation of ovarian function. The study included 35 women divided into two groups of women aged 30 or younger and those older than 30. Hormone concentrations were assessed by measurements of lutropin (LH ), follitropin (FSH), estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG) and AMH on cycle day 3-5 (follicular phase); and LH , FSH and E2 on cycle day 13-15 (ovulation). Progesterone level was determined on cycle day 19-23 (luteal phase). Median age differed significantly between the two groups of study subjects (p=0.001). Study results confirmed regular ovarian response to physiological gonadotropin stimulation, which is the assumption for normo-ovulatory cycles. Some decrease in the mean serum AMH levels was recorded in women over 30 years of age, although the difference was not statistically significant (p=0.0693). There was no statistically significant difference in serum AMH concentrations between follicular phase and ovulation in study women (p=0.3124). Our preliminary results, although obtained in a limited number of women, support the diagnostic value of AMH as a reliable marker of ovarian reserve.Anti-Müllerov hormon (AMH ) sintetizira se u Sertolijevim stanicama testisa u muškaraca i granuloza stanicama jajnika u žena. Dosadašnje studije dokazale su važnost određivanja anti-Müllerovog hormona kao novog biljega u procjeni ovarijske rezerve. Također, ranije objavljeni rezultati pokazali su neznačajnu promjenjivost koncentracija AMH u serumu tijekom menstruacijskog ciklusa. Cilj ovoga preliminarnog istraživanja bio je ustanoviti odnos koncentracije AMH u žena s redovitim ciklusima i normalnim hormonskim statusom u odnosu na njihovu dob. Uključeno je 35 žena podijeljenih u skupine od 30 godina i mlađih te starijih od 30 godina. Hormonsku regulaciju menstruacijskog ciklusa smo potvrdili određivanjem koncentracija lutropina (LH ), folitropina (FSH), estradiola (E2), ukupnog i slobodnog testosterona (T), proteinskog nosača spolnih hormona (SHBG) te AMH u folikularnoj fazi ciklusa (3.-5. dan). U ovulacijskoj fazi (13.-15. dan) određivali smo koncentracije LH , FSH, E2 i AMH , odnosno progesterona (P) u luteinskoj fazi (20.-23. dan). Medijani dobi u mlađoj i starijoj skupini bili su statistički značajno različiti (p=0,001). Rezultati su potvrdili urednu hormonsku regulaciju djelovanja osovine hipofiza-jajnici u izabranih ispitanica. Ustanovili smo relativno niže koncentracije AMH u žena iznad 30 godina u usporedbi sa skupinom mlađih, iako razlika nije bila statistički značajna (p=0,0693). Također, prosječne koncentracije AMH u folikularnoj fazi i ovulaciji nisu bile statistički značajno različite (p=0,3124). Preliminarni rezultati ovoga istraživanja, iako na ograničenom broju ispitanica, podupiru dijagnostičku važnost AMH kao osjetljivog biljega u procjeni ovarijske rezerve

The impact of temporal variability of biochemical markers PAPP-A and free β-hCG on the specificity of the first-trimester Down syndrome screening: a Croatian retrospective study

<p>Abstract</p> <p>Background</p> <p>The variability of maternal serum biochemical markers for Down syndrome, free β-hCG and PAPP-A can have a different impact on false-positive rates between the 10+0 and 13+6 week of gestation. The study population comprised 2883 unaffected, singleton, spontaneously conceived pregnancies in Croatian women, who delivered apparently healthy child at term. Women were separated in 4 groups, dependently on the gestational week when the analyses of biochemical markers were performed. The concentrations of free β-hCG and PAPP-A in maternal serum were determined by solid-phase, enzyme-labeled chemiluminiscent immunometric assay (Siemens Immulite). Concentrations were converted to MoMs, according to centre-specific weighted regression median curves for both markers in unaffected pregnancies. The individual risks for trisomies 21, 18 and 13 were computed by Prisca 4.0 software.</p> <p>Findings</p> <p>There were no significant differences between the sub-groups, regarding maternal age, maternal weight and the proportion of smokers. The difference in log₁₀MoM free β-hCG values, between the 11^thand 12^thgestational week, was significant (p = 0.002). The difference in log₁₀MoM PAPP-A values between the 11^thand 12^th, and between 12^thand 13^thweek of gestation was significant (p = 0.006 and p = 0.003, respectively). False-positive rates of biochemical risk for trisomies were 16.1% before the 11^thweek, 12.8% in week 12^th, 11.9% in week 13^thand 9.9% after week 13^th. The differences were not statistically significant.</p> <p>Conclusions</p> <p>Biochemical markers (log₁₀MoMs) showed gestation related variations in the first-trimester unaffected pregnancies, although the variations could not be attributed either to the inaccuracy of analytical procedures or to the inappropriately settled curves of median values for the first-trimester biochemical markers.</p

COMBINED ULTRASOUND-BIOCHEMICAL SCREENING OF FETAL TRISOMIA IN THE FIRST TRIMESTER AND DOUBLE BIOCHEMICAL SCREENING IN THE SECOND TRIMESTER AT NONRISK PREGNANCIES

Cilj rada: Usporediti uspješnost primjene probirnih testova aneuploidija u prvom i drugom tromjesečju trudnoće. Ispitanice i metode: Istraživanu skupinu činilo je 374 trudnica s kombiniranim ultrazvučno-biokemijskim testom u prvom, odnosno dvostrukim biokemijskim testom u drugom tromjesečju. Sve su trudnoće bile jednoplodne i urednog ishoda. U probiru prvog tromjesečja korišteni su biokemijski biljezi u serumu trudnica: plazmatski protein pridružen trudnoći (PAPP-A) i slobodna B-podjedinica humanog korionskog gonadotropina (slobodni B-hCG), uz ultrazvukom izmjerenu debljinu nuhalnog nabora (NT) i dužinu tjeme-trtica (CRL) u ploda. U dvostrukom biokemijskom probiru drugog tromjesečja korišteni su biokemijski biljezi: alfa-fetoprotein (AFP) i slobodni B-hCG, a gestacija je procijenjena prema ultrazvučnoj biometriji. Rezultati: Povećani ultrazvučno-biokemijski rizik trisomije 21 u 1. tromjesečju trudnoće ustanovili smo u 30 trudnica (8.0%). Od ukupnog broja, 70 ispitanica (18.7%) imalo je povećani rizik obzirom na biokemijske biljege u ¬prvom, odnosno njih 56 (15.0%) obzirom na biokemijske biljege u drugom tromjesečju trudnoće. Izvršeno je ukupno 30 postupaka amniocenteze. Od toga je u 19 trudnica (63.3%) indikacija postavljena na osnovi kombiniranog probirnog testa. Nadalje, amniocenteza je izvršena u 11 trudnica (28.2%) zbog povećanog rizika u dvostrukom biokemijskom probiru drugog tromjesečja. Udjel lažno-pozitivnih razultata u kombiniranom probiru prvog tromjesečja bio je statistički značajno niži, nego u biokemijskom probiru drugog tromjesečja (B2=12.02, p=0.0005). Ustanovili smo značajnu pozi¬tivnu povezanost log10 MoM slobodnog B-hCG između prvog i drugog tromjesečja (r2=0.403, p<0.0001). Nismo ustanovili značajnu povezanost između ostalih biokemijskih biljega u prvom, odnosno, drugom tromjesečju. Zaključak: Rezultati našeg istraživanja su pokazali značajno veću specifičnost ranog kombiniranog probirnog testa aneuploidija u odnosu na biokemijski probirni test u prvom, kao i u drugom tromjesečju. Mogućnosti izbora pojedinih probirnih testova trebale bi biti usklađene sa stavovima i potrebama samih trudnica, kao i sa smjernicama koje su preporučile nadležne institucije za fetalnu medicinuObjective: To evaluate the performance of screening tests for aneuploidy in the first and second trimesters of pregnancy in Croatian pregnant women. Study Design and Methods: Study population comprised 374 pregnant women who underwent the combined ultrasound-biochemical in the first and double-test in the second trimester of pregnancy, respectively. All were singleton pregnancies with normal outcomes. The first-trimester screening was performed combining serum markers, pregnancy associated plasma protein-A (PAPP-A) and free B-subunit of human chorionic gonado¬tropin (free B-hCG) with fetal nuchal translucency thickness (NT) and crown-rump length (CRL), measured by ultrasound. For the second-trimester screening, maternal serum alpha-fetoprotein and free B-hCG were used as biochemical markers in relation to fetal biometry diagnosed by ultrasound. Results: In 30 pregnant women (8.0%) elevated risk for trisomy 21 was found after combined ultrasound-biochemical screening. Out of total, 70 pregnant women (18.7%) were classified ’at risk’ on the basis of biochemical markers in the first and 56 (15.0%) in the second trimester. In 30 pregnant women amniocentesis was performed. In 19 cases (63.3%) the indication was elevated risk in the first-trimester combined test. In 11 women (28.2%) amniocentesis is recommended because of the elevated second-trimester biochemical risk. The proportion of false-positive results in combined first-trimester screening test was significantly lower than with second-trimester biochemical markers (B2=12.02, p=0.0005). We found the significant positive relationship between log10 MoM F B-hCG in the first and second trimester (r2=0.403, p<0.0001). There was no significant relationship between PAPP-A and second-trimester biochemical markers. Conclusion: Results of this preliminary study confirmed better specificity of the combined first-trimester screening in relation to biochemical screening in the second trimester of pregnancy. The decision and choice of the most appropriate screening test should consider woman’s personal attitude and preferences, as well as follow the guidelines recommended by the competent associations for the fetal medicine

COMBINED ULTRASOUND AND BIOCHEMICAL SCREENING FOR FETAL ANEUPLOIDY AT 10 – 14 WEEKS OF PREGNANCY: FIRST RESULTS OF TEST PERFORMANCE IN CROATIA

Sažetak. Cilj rada. Retrospektivna studija nakon primjene kombiniranog ultrazvučno-biokemijskog testa probira trisomija u prvom tromjesečju trudnoće. Metode. Od veljače 2006. do srpnja 2008. godine probir je učinjen u 1112 trudnica između 10. i 14. tjedna trudnoće. Individualni rizik trisomije 21, 18 i 13 izračunavali smo kombinacijom dobnog rizika trudnice, ultrazvučnih biljega u ploda (debljina nuhalnog nabora – NT, udaljenosti tjeme-trtica – CRL) te biokemijskih biljega u serumu trudnice (slobodni -hCG i PAPP-A), pomoću licenciranog računalnog programa (Typolog). Koncentracije biokemijskih biljega smo određivali imunometrijskom kemiluminiscentnom metodom (IMMULITE). Biokemijske biljege, kao i NT u odnosu na CRL, izrazili smo u obliku višekratnika MoM, u odnosu na dnevne regresijske medijane za odgovarajuću gestaciju u neugroženim trudnoćama. Rezultate smo obradili nakon dovršenih svih ispitanih trudnoća. Ukupno su 62 testirane trudnice imale povećani kombinirani rizik trisomije 21, od kojih je 10 trudnica imalo i povećani rizik trisomije 18/13. Četiri trisomije 21 i jedna trisomija 18 otkrivene su prenatalnom dijagnozom; stopa detekcije bila je 100% (5/5). U trudnica s povećanim rizikom u probiru učinjeno je 7 biopsija koriona i 38 ranih amniocenteza. Udio lažno-pozitivnih rezultata bio je 5.1%. Zaključak. Prvi rezultati provođenja kombiniranog probirnog testa u Hrvatskoj potvrdili su visoku osjetljivost i veću specifičnost, u poredbi s biokemijskim probirnim testom u drugom tromjesečju trudnoće.Objective. Retrospective study of the results of the first-trimester combined screening for fetal trisomies with ultrasound and biochemical markers. Methods. In the period from February 2006 to July 2008, a total of 1112 pregnant-women underwent screening between the 10th and 14th gestational week. Individual risk for trisomies 21, 18 and 13, combining maternal age, ultrasonography (nuchal translucency, crown-rump length) and serum biochemical analytes (free -hCG, PAPP-A) was computed by means of licensed Typolog software. Concentrations of biochemical markers were determined by chemiluminiscent immunometric assay (IMMULITE). Both biochemical markers, as well as NT, were expressed as Multiples of the Median (MoM), based on the regressed medians of the corresponding gestational age in unaffected pregnancies. Results. All studied pregnancies were followed up to term. A total of 62 pregnant women were categorized as high-risk for trisomy 21, and 10 of them had also an elevated risk for trisomies 18/13, respectively. Four trisomies 21 and one trisomy 18 were detected through combined test and confirmed with prenatal diagnostic procedure. Detection rate was 100%. In those with high risk, 7 chorionic villi sampling and 38 amniocenteses were performed. False-positive rate was 5.1%. Conclusion. The results of the first-trimester screening in Croatia confirmed high sensitivity and better specificity of the combined ultrasonic and biochemical markers, in relation with the second-trimester biochemical screening test

COMBINED ULTRASOUND AND BIOCHEMICAL SCREENING FOR FETAL ANEUPLOIDY AT 10 – 14 WEEKS OF PREGNANCY: FIRST RESULTS OF TEST PERFORMANCE IN CROATIA

Sažetak. Cilj rada. Retrospektivna studija nakon primjene kombiniranog ultrazvučno-biokemijskog testa probira trisomija u prvom tromjesečju trudnoće. Metode. Od veljače 2006. do srpnja 2008. godine probir je učinjen u 1112 trudnica između 10. i 14. tjedna trudnoće. Individualni rizik trisomije 21, 18 i 13 izračunavali smo kombinacijom dobnog rizika trudnice, ultrazvučnih biljega u ploda (debljina nuhalnog nabora – NT, udaljenosti tjeme-trtica – CRL) te biokemijskih biljega u serumu trudnice (slobodni -hCG i PAPP-A), pomoću licenciranog računalnog programa (Typolog). Koncentracije biokemijskih biljega smo određivali imunometrijskom kemiluminiscentnom metodom (IMMULITE). Biokemijske biljege, kao i NT u odnosu na CRL, izrazili smo u obliku višekratnika MoM, u odnosu na dnevne regresijske medijane za odgovarajuću gestaciju u neugroženim trudnoćama. Rezultate smo obradili nakon dovršenih svih ispitanih trudnoća. Ukupno su 62 testirane trudnice imale povećani kombinirani rizik trisomije 21, od kojih je 10 trudnica imalo i povećani rizik trisomije 18/13. Četiri trisomije 21 i jedna trisomija 18 otkrivene su prenatalnom dijagnozom; stopa detekcije bila je 100% (5/5). U trudnica s povećanim rizikom u probiru učinjeno je 7 biopsija koriona i 38 ranih amniocenteza. Udio lažno-pozitivnih rezultata bio je 5.1%. Zaključak. Prvi rezultati provođenja kombiniranog probirnog testa u Hrvatskoj potvrdili su visoku osjetljivost i veću specifičnost, u poredbi s biokemijskim probirnim testom u drugom tromjesečju trudnoće.Objective. Retrospective study of the results of the first-trimester combined screening for fetal trisomies with ultrasound and biochemical markers. Methods. In the period from February 2006 to July 2008, a total of 1112 pregnant-women underwent screening between the 10th and 14th gestational week. Individual risk for trisomies 21, 18 and 13, combining maternal age, ultrasonography (nuchal translucency, crown-rump length) and serum biochemical analytes (free -hCG, PAPP-A) was computed by means of licensed Typolog software. Concentrations of biochemical markers were determined by chemiluminiscent immunometric assay (IMMULITE). Both biochemical markers, as well as NT, were expressed as Multiples of the Median (MoM), based on the regressed medians of the corresponding gestational age in unaffected pregnancies. Results. All studied pregnancies were followed up to term. A total of 62 pregnant women were categorized as high-risk for trisomy 21, and 10 of them had also an elevated risk for trisomies 18/13, respectively. Four trisomies 21 and one trisomy 18 were detected through combined test and confirmed with prenatal diagnostic procedure. Detection rate was 100%. In those with high risk, 7 chorionic villi sampling and 38 amniocenteses were performed. False-positive rate was 5.1%. Conclusion. The results of the first-trimester screening in Croatia confirmed high sensitivity and better specificity of the combined ultrasonic and biochemical markers, in relation with the second-trimester biochemical screening test

Pregnant Women’s Knowledge and Attitudes to Prenatal Screening for Fetal Chromosomal Abnormalities: Croatian Multicentric Survey

We aimed to assess opinion and preferences of Croatian pregnant women regarding the prenatal screening tests for trisomies. The study was conducted in Zagreb, Split, Čakovec, Nova Gradiška, Gospić and Zlatar. It was organized in the public primary healthcare centers, among the pregnant volunteers during their first visit to an antenatal clinic (7–12 weeks pregnant). The respondents filled anonymous questionnaire reflecting their knowledge and attitudes to the screening options. In total, 437 completed questionnaires were selected. The average maternal age and the level of education differed significantly between the respondents in the respective cities (P<0.001). Of the respondents with positive attitude towards screening, the majority would prefer the first-trimester combined test (160/219; 73.1%), while 37/219 (16.9%) opted for the second-trimester biochemical screening. The remaining 22/219 (10.0%) would accept only the ultrasound screening. Among the 224 respondents, who would accept the combined first-trimester test, 95 (42.4%) held a college and university degree, whereas among 59 women, who would choose the second-trimester biochemical screening, 14 were highly educated (23.7%). The difference was statistically significant (P=0.016). The univariate regression analysis showed that age, level of education and previous information were significant variables predictive for the choice of the test; the level of education and previous knowledge remained significant in the multivariate model. The survey has revealed some of the points that should be improved in the future concept of screening program in Croatia. Health professionals should persist to mend women’s knowledge about prenatal screening, taking into consideration women’s preferences as well

Biochemical Screening of Fetal Aneuploidies and Neural Tube Defects by »Double-Test« in Croatia: A 10 Years’ Experience

The aim of the study is to investigate the efficiency of the second-trimester biochemical screening, with maternal serum alpha-fetoprotein (MS-AFP) and free b-subunit of human chorionic gonadotropin (free b-hCG), during the ten-year period. The study included 11,292 of pregnant women between the 15th and 18th gestational week, who underwent screening from November 1996 to December 2006. The risk for trisomy 21 and trisomy 18 were calculated by computer software, based on a model which generated the final risk for fetal aneuploidies from the pregnant woman’s a priori age risk and the likelihood ratio of the distribution of the biochemical markers, according to the second-trimester gestation. With the cut-off value of the final risk 1:250, the detection rate for trisomy 21 was 75% (21/28). In women less than or equal to 35, the detection was 57.1% (8/14) and 92.9% (13/14) in those over 35 years, respectively. The detection rate of trisomy 18 was 50% (2/4). The results confirmed that the implementation of double-test, as non-invasive screening for fetal aneuploidies, should be accepted as a complementary method of antenatal care