Prenatal screening for trisomy 18 with free beta human chorionic gonadotrophin as a marker.

OBJECTIVE--To determine the relation between maternal serum alpha fetoprotein and free beta human chorionic gonadotrophin concentrations in pregnancies complicated by trisomy 18 and establish whether prenatal biochemical screening for this condition could be developed in a way similar to that proposed for trisomy 21. DESIGN--Serum alpha fetoprotein and free beta human chorionic gonadotrophin concentrations in women with singleton pregnancies affected by cytogenetically confirmed trisomy 18, uncomplicated by neural tube defect or ventral wall defect, were identified from prospective trisomy 21 screening programmes. Additionally, stored maternal serum from similar pregnancies was analysed retrospectively. Analyte concentrations from singleton unaffected pregnancies were identified from a prospective screening programme as controls. Statistical parameters of the affected and unaffected populations were compiled. SETTING--Biochemical screening laboratories in Britain and the United States. SUBJECTS--52 women with singleton pregnancies complicated by trisomy 18; control population of 6661 women with unaffected singleton pregnancies. MAIN OUTCOME MEASURES--Median values of each analyte and their distribution in the affected and unaffected populations; detection rate of trisomy 18 and the false positive rate. RESULTS--Maternal serum alpha fetoprotein and free beta human chorionic gonadotrophin concentrations were significantly lower in pregnancies complicated by trisomy 18 (median values 0.71 and 0.37 respectively). By using a multivariate risk algorithm incorporating maternal age risk of trisomy 18 and the concentration of the two biochemical markers it was predicted that 50% of trisomy 18 cases (unaffected by neural tube defect or ventral wall defect) could be detected with a 1% false positive rate. CONCLUSION--Second trimester biochemical screening for trisomy 18 could be a valuable addition to trisomy 21 screening programmes.     

Trial of support treatment with human chorionic gonadotrophin in the luteal phase after treatment with buserelin and human menopausal gonadotrophin in women taking part in an in vitro fertilisation programme.

OBJECTIVE--To evaluate the effect of support with human chorionic gonadotrophin in the luteal phase in women taking part in an in vitro fertilisation programme after buserelin and human menopausal gonadotrophin were used to hyperstimulate their ovaries. DESIGN--Controlled group comparison. SETTING--Outpatient department of a private hospital. PATIENTS--115 Women with indications for in vitro fertilisation, all of whom had at least one embryo transferred. INTERVENTIONS--After suppression of the pituitary with buserelin the ovaries of all the women were stimulated with human menopausal gonadotrophin on day 4 of the luteal phase. Human chorionic gonadotrophin (10,000 IU) was given to induce ovulation, and oocytes were recovered 34 hours later. Embryos were transferred 46 to 48 hours after insemination. Women who had received the 10,000 IU of human chorionic gonadotrophin on a date that was an uneven number (n = 61) were allocated to receive support doses of 2500 IU human chorionic gonadotrophin three and six days after that date. The remaining 54 women did not receive hormonal support. END POINT--Determination of the rates of pregnancy. MEASUREMENTS and main results--Support with human chorionic gonadotrophin did not significantly alter the progesterone or oestradiol concentrations in the early or mid-luteal phase. The mean (range) progesterone concentrations in the late luteal phase in women who did not become pregnant were, however, significantly higher in those who received support (16(9-110) nmol/l nu 8(4-46) nmol/l), and the luteal phase was significantly longer in this group (14 days nu 12 days). The rate of pregnancy was significantly higher in the women who received support than in those who did not (25/61 nu 8/54). CONCLUSIONS--When buserelin and human menopausal gonadotrophin are used to hyperstimulate ovaries support with human chorionic gonadotrophin in the luteal phase has a beneficial effect on in vitro fertilisation.     

Improvement of in vitro fertilisation after treatment with buserelin,an agonist of luteinising hormone releasing hormone

Treatment with buserelin, an agonist of luteinising hormone releasing hormone, and human menopausal gonadotrophin was compared with the conventional treatment of clomiphene citrate and human menopausal gonadotrophin in the outcome of in vitro fertilisation. Seventy seven infertile women had 83 cycles of treatment with buserelin and human menopausal gonadotrophin, and concurrently another 328 infertile women were treated with clomiphene citrate and human menopausal gonadotrophin. Seven (8%) cycles were cancelled owing to inadequate superovulation or ovarian hyperstimulation in the women receiving buserelin and 103 (31%) were cancelled because of poor follicular development in those receiving clomiphene citrate. The mean number of oocytes recovered was significantly higher with buserelin (9·5 (SD 4·5) v 5·5 (2·2)) as was the mean number of embryos obtained (4·3 (2·4) v 2·9 (1·7)). Significantly more women who had an embryo transfer became clinically pregnant after treatment with buserelin (53% (30/57) v 30% (48/159), or 36% v 14% of treatment cycles). Altogether 33% (10) of pregnancies in women treated with buserelin were multiple compared with 23% (11) in those treated conventionally. Of the 17 completed pregnancies in women treated with buserelin, 11 resulted in the birth of live babies (eight singletons, two sets of twins, and one set of triplets) and six failed, five before 12 weeks'' gestation and one at 22 weeks. The 13 continuing pregnancies (32 weeks) were eight singletons, two sets of twins, and three sets of triplets. Of the 48 completed pregnancies in women treated with clomiphene citrate, 35 resulted in the birth of live babies (26 singletons, five sets of twins and four sets of triplets) and 13 failed, eleven before 12 weeks'' gestation and two by 27 weeks.Buserelin increased the chance of pregnancy after in vitro fertilisation compared with conventional treatment, but the risk of multiple pregnancy may be increased.     

High incidence of preterm births and early losses in pregnancy after in vitro fertilisation. Australian in vitro fertilisation collaborative group.

A fertilisation cohort of 244 pregnancies resulting from in vitro fertilisation was reported to a national register by eight units specialising in in vitro fertilisation. Early pregnancy losses were high, with 5% tubal ectopic pregnancies, 18% biochemical pregnancies, and an incidence of spontaneous abortion of 27%. Among pregnancies of at least 20 weeks'' gestation 22% were multiple, with 26 pairs of twins and four sets of triplets. The incidence of preterm births was more than three times higher than in the general population. Low birthweight rates were also higher, owing both to preterm births and to multiple pregnancies. The sex ratio and the incidence of major congenital malformations were similar to those in naturally conceived pregnancies. In this series the high fetal losses at all stages of pregnancy suggested maternal reproductive causes and should not be interpreted as being due to factors peculiar to in vitro fertilisation. Further analysis will be necessary when larger numbers are available.     

A maternal serum screen for trisomy 18: an extension of maternal serum screening for Down syndrome.

The feasibility of extending second-trimester maternal blood screening for Down syndrome so as to include screening for trisomy 18 was examined using stored maternal serum samples collected for neural tube-defect screening. There were 12 samples from trisomy 18 pregnancies and 390 controls. The median maternal serum concentration of alpha-fetoprotein, free alpha-subunit human chorionic gonadotrophin, free beta-subunit human chorionic gonadotrophin, intact human chorionic gonadotrophin, total estriol, unconjugated estriol, estradiol, human placental lactogen, and progesterone were lowered in those pregnancies affected by trisomy 18 when compared with unaffected pregnancies matched for racial origin, maternal age, gestational age, and sample-storage duration. At an estimated odds risk of 1:400, 83.3% of affected pregnancies were detected using an algorithm which combines the maternal age-related risk with the maternal serum concentrations of unconjugated estriol, free alpha-subunit human chorionic gonadotrophin, free beta-subunit human chorionic gonadotrophin, estradiol, and human placental lactogen. The associated false-positive rate was 2.6%. At high risk odds of 1:10, the detection rate was 58.3%, with an associated false-positive rate of 0.3%. beta-Subunit human chorionic gonadotrophin and unconjugated estriol were the most powerful discriminators. It is possible to incorporate into existing Down syndrome screening programs an algorithm for detecting trisomy 18 with high sensitivity and specificity.     

Maternal serum screening for Down's syndrome in early pregnancy.

The possibility of improving the effectiveness of antenatal screening for Down''s syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Down''s syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Down''s syndrome in the United Kingdom from about 900 a year to about 350 a year.     

Serum oestradiol, progesterone, chorionic gonadotrophin and prolactin concentrations during pregnancy in the Bolivian squirrel monkey (Saimiri sciureus)

Concentrations of chorionic gonadotrophin gradually increased during early pregnancy, reached maximum values at mid-gestation, then declined to low levels. Oestradiol-17 beta concentrations were relatively low (300-600 pg/ml) during early pregnancy, increased thereafter to high levels (10-35 ng/ml), and then appeared to decline towards term. Concentrations of progesterone were constant (100-200 ng/ml) for the first 15 weeks of gestation, suggesting that sequential measurements of progesterone could be used to diagnose early pregnancy. Prolactin concentrations rose during pregnancy, reaching maximum values at term.     

The effect of human chorionic gonadotrophin and exogenous progesterone on luteal function during early pregnancy in pony mares

Previous reports have indicated that repeated administrations of human chorionic gonadotrophin (hCG) to pony mares before day 38 of gestation caused pregnancy failure, but that this could be prevented by the prior or simultaneous administration of progesterone. The present paper describes the circulating progestagen concentrations during these experiments, and shows that pregnancy failure resulted from luteolysis after hCG administration. Most of the mares which received progesterone maintained their pregnancies after hCG injection, but progestagen concentrations fell, suggesting that partial lysis of the corpus luteum occurred. After day 38 of gestation repeated doses of hCG had no effect on plasma progestagen concentrations.     

Assessment of fetal number, and fetal and placental viability throughout pregnancy in cattle

Production of identical twin calves by embryo demisection requires a reliable system for continual monitoring of pregnancy. Both halves of bisected embryos were replaced nonsurgically into one uterine horn on Day 7 in 80 recipients. Monthly blood sampling began on Day 22 of pregnancy and transrectal echography took place between 50 and 80 days. Fifty-four recipients had elevated plasma progesterone concentrations on Day 22 (67% pregnancy rate). Of 21 pregnancies diagnosed as twins by echography, 15 live sets were born, 3 singles accompanied by a stillbirth, and 3 complete abortions. Twenty-five singleton pregnancies resulted in 23 live calves, 1 still-birth and 1 abortion. It was not possible to monitor echographically the remaining 8 pregnancies. At all stages of pregnancy studied, mean concentrations of bovine pregnancy-specific protein B (bPSPB) and estrone sulphate were higher (P<0.01) in twin (n = 17) than in single (n = 26) pregnancies, but the high individual variation obviated any predictive value for fetal number. Although bPSPB and estrone sulphate concentrations were positively correlated at most stages of normal pregnancies after Day 100, divergence was observed in the unsuccessful pregnancies between the concentrations of all 3 hormones, suggesting synthesis/release is under independent control. Measurement of bPSPB may be useful for prediction of fetal well-being, whereas estrone sulphate may reflect placental viability.     

Obstetric outcome in donor oocyte pregnancies: a matched-pair analysis

ABSTRACT: BACKGROUND: To investigate the obstetrical and perinatal impact of oocyte donation, a cohort of women who conceived after OD was compared with a matched control group of women who became pregnant through in vitro fertilisation with autologous oocytes (AO). METHODS: A matched-pair analysis has been performed at the Centre for Reproductive Medicine of the UZ Brussel, Dutch speaking Free University of Brussel. A total of 410 pregnancies resulted in birth beyond 20 weeks of gestation occurring over a period of 10 years, including 205 oocyte donation pregnancies and 205 ICSI pregnancies with autologous oocytes (AO). Patients in the OD group were matched on a one-to-one basis with the AO group in terms of age, ethnicity, parity and plurality. Matched groups were compared using paired t-tests for continuous variables and McNemar test for categorical variables. A conditional logistic regression analyses was performed adjusting for paternal age, age of the oocyte donor, number of embryos transferred, and singleton/twin pregnancy. RESULTS: Oocyte donation was associated with an increased risk of pregnancy induced hypertension (PIH) (matched OR: 1.502 CI: 1.024-2.204), and first trimester bleeding (matched OR: 1.493 CI: 1.036-2.15). No differences were observed between the two matched groups with regard to gestational age, mean birth weight and length, head circumference and Apgar scores. CONCLUSIONS: Oocyte donation is associated with an increased risk for PIH and first trimester bleeding independent of the recipients? age, parity and plurality, and independent of the age of the donor or the partner. However, oocyte donation has no impact on the overall perinatal outcome.     

Maternal serum progesterone, 17 beta-estradiol and estriol are increased in pregnancies which follow treatment with human menopausal gonadotropins: effects of multiple gestation and maternal endocrine status

A high incidence of premature labor, incompetent cervix and fetal wastage occurs in multiple gestations which follow treatment with human menopausal gonadotropins (HMG). In order to determine the effect of treatment with HMG on hormone secretion in human pregnancy, progesterone (PROG), 17 beta-estradiol (E2), estriol (E3) and human chorionic gonadotropin (hCG) were determined by radioimmunoassay in 341 serum specimens from 229 normal singleton pregnancies and in 79 serum specimens from 20 pregnancies following induction of ovulation with HMG in women with either hypothalamic amenorrhea (HA) or the polycystic ovary syndrome (PCO). Fitting equations were found for the log transformed normal values and the residuals were obtained by subtraction of the predicted normal values from the log transformed values observed in the HMG pregnancies. In pregnancies which followed treatment with HMG, PROG and E2 were initially elevated above normal. As pregnancy progressed, the deviation from normal became proportionately less. PROG (P less than 0.025) was lower and E2 (P less than 0.025) and E3 (P less than 0.05) were higher in PCO pregnancies than in HA pregnancies. Multiple gestation produced increases in PROG (P less than 0.005), E2 (P less than 0.005) and E3 (P less than 0.001) in comparison to singleton pregnancies.     

Clinical implications of developments in in vitro fertilisation.

During February 1979 to December 1983, 831 infertile couples were treated by in vitro fertilisation and embryo transfer. The problems they faced included deciding on the number of oocytes to be collected at laparoscopy, the numbers to be donated or fertilised, the numbers of embryos to be transferred and frozen, and whether abnormal embryos should be used for research or discarded. The 831 patients received a total of 1530 treatment cycles. Of the 763 patients for whom complete data were available, 136 (17.8%) became pregnant. The rate of pregnancy, however, increased dramatically from 7.4% when only one embryo was transferred to 21.1% and 28.1% when two and three embryos were transferred, respectively. The chance of multiple pregnancy also increased with the number of embryos transferred, but the risk (2% for twins) was far outweighed by the relatively poor result after transferring a single embryo. Out of 40 embryos freeze-thawed, 23 survived thawing and were transferred; of these, 4 (17%) resulted in pregnancy. Thirty four transfers of donor oocyte embryos also resulted in four pregnancies (12%), but two of these ended in abortion. Neither microscopy nor any other available test can determine the potential of an oocyte to result in pregnancy, so that discarding oocytes that may look abnormal simply reduces the chances of conception--both for the patient and for any prospective recipient of donor oocyte embryos. In any case, abnormal embryos tend to die when growth is allowed to continue in vitro. Probably all oocytes harvested from a patient should be inseminated and the utilisation of the embryos decided once the number developed is known.     

Repeatability of events during spontaneous and gonadotrophin-induced oestrus in bitches.

Oestrus induction using equine chorionic gonadotrophin and human chorionic gonadotrophin was successful in five out of six bitches, although the first day of increased plasma progestagen concentration differed considerably between bitches. Induced oestrous periods differed from spontaneous cycles in the timing of vaginal epithelial cell cornification; plasma oestrogen concentrations were generally greater and progestogen concentrations were less in induced cycles. These results suggest that this schedule of oestrus induction would not be suitable for allowing mating on a predetermined day.     

Risk assessment adjusted for gestational age in maternal serum screening for Down's syndrome.

OBJECTIVE--To investigate the relation between errors in calculation of gestational age and assessment of risk of Down''s syndrome and to analyse the implications for screening programmes. DESIGN--Retrospective analysis of dating of gestational age by menstrual history v ultrasound scan. Computer program with maternal age and concentrations of alpha fetoprotein and free beta human chorionic gonadotrophin to calculate risk for a range of expected dates of delivery. Computer simulated prospective application of new screening programme. SETTING--Teaching hospitals in Nottingham. SUBJECTS--31,561 women with singleton pregnancies with gestational age based on routine ultrasound scan. Computer simulation of 20,000 women in three age ranges (up to 37; up to 40; all). MAIN OUTCOME MEASURES--Distribution of error between gestational age based on ultrasound scan v menstrual history. Proportion of women in the population who require precise dating of pregnancy; proportion of women who require amniocentesis. RESULTS--With gestational age derived from ultrasound scan as reference the 95% confidence interval for gestational age by menstrual history was -27 to +9 days. A screening programme for Down''s syndrome for women up to age 40 would yield a low risk (< 1:250) for this range of days in 86.0% of cases. The 14.0% of women remaining would have one or more high risk values in their report and would thus require an ultrasound scan for precise dating of the pregnancy; 30% of these--that is, 3.7% of the screened population--would be identified as high risk and require consideration for amniocentesis. CONCLUSIONS--Screening programmes for Down''s syndrome require the facility for precise dating of pregnancy to improve the accuracy of risk assessment. This can be achieved without introducing additional scans for early dating in the whole population but by selecting only those cases (about 14%) when an error in dates is likely to affect the risk of Down''s syndrome.     

Pregnancy in patients presenting with hyperprolactinaemia.

Ninety-two pregnancies occurred in 76 hyperprolactinaemic patients treated with bromocriptine. Half conceived within three months of attempted conception. There was no evidence of an increased rate of spontaneous abortion, fetal abnormality, or multiple pregnancy; the three twin pregnancies occurred in women who were additionally treated with clomiphene and human chorionic gonadotrophin. Thirty-one patients had radiological evidence of a pituitary tumour; 14 with major radiograph changes in the pituitary fossa or serum prolactin concentrations greater than 100 ng/ml received pituitary irradiation before conception. None of the latter showed evidence of enlargement of the tumour during pregnancy. In contrast two of the four patients with similar tumours but who were not irradiated developed visual field defects, one with gross destruction of the pituitary fossa. Prophylactic treatment to limit subsequent tumour expansion during pregnancy in patients with prolactinomas is indicated, and pituitary irradiation before conception appears to be a safe and effective method to achieve this goal.     

Lanosterol 14alpha-demethylase expression in the mouse ovary and its participation in cumulus-enclosed oocyte spontaneous meiotic maturation in vitro

The expression of lanosterol 14alpha-demethylase (LDM) in the mouse ovary after gonadotrophin administration was examined and the action of follicle fluid meiosis activating sterol (FF-MAS), derived from lanosterol by the action of LDM, on oocyte spontaneous maturation was also evaluated in cumulus cell enclosed oocytes (CEOs). Expression of LDM was primarily in oocytes in primordial and secondary follicles prior to administration of gonadotrophins, but obvious LDM expression was apparent in ovarian somatic cells 48 h after administration of equine chorionic gonadotrophin (eCG), especially in luteal and cumulus cells 54 h after eCG or 48 h after eCG plus 6 h after human chorionic gonadotrophin (hCG). The LDM expression in oocytes was only slightly elevated in larger growing follicles after eCG treatment. On the contrary, 48 h after hCG treatment, the elevated expression of LDM was only detected in interstitial cells. Therefore, eCG may be the primary gonadotrophin for LDM expression, and furthermore for production of FF-MAS in mouse cumulus cells (which are indispensable for oocyte maturation in vivo). Conversely, inhibitors of LDM, either 40 microM azalanstat or 50 microM RS-21745, significantly inhibited oocyte germinal vesicle breakdown (GVB) after 4h of in vitro culture; GVB rates decreased to 14 or 20%, compared to 90% in spontaneous maturation, respectively. There was no significant increase in GVB in CEOs following specific inhibitor of sterol Delta14-reductase and Delta7-reductase, AY9944-A-7 (5-100 microM), until marked oocytes degeneration appeared (50 microM). The phenomena may be ascribed to slow, passive accumulation of FF-MAS by AY9944-A-7, which cannot be associated with fast spontaneous progression. Furthermore, in spontaneous-matured CEOs, LDM was expressed preferentially in cumulus cells instead of oocytes. Therefore, FF-MAS may have a positive role in the spontaneous maturation of CEOs. In conclusion, there was an eCG-dependent dual LDM expression pattern on both oocytes and somatic cells in growing follicles in vivo, which may increase LDM expression and FF-MAS production in cumulus cells for oocyte maturation. For the first time, the inhibitory effect of LDM inhibitors on spontaneous maturation, together with the strong LDM expression in spontaneous matured CEOs, indicated that FF-MAS produced by cumulus cells might participate in spontaneous maturation of mouse CEOs.     

Progesterone and estradiol-17beta in the peripheral plasma of Brahman cows with single and twin pregnancies

Peripheral plasma samples from Brahman cows with single and twin pregnancies were assayed for progesterone and estradiol-17beta throughout pregnancy. The twin pregnancies were obtained by transfer of Friesian embryos to inseminated single-ovulating Brahman cows. The twin-bearing cows had significantly higher levels of progesterone at 8 and 36 weeks of pregnancy. There were no differences in estradiol-17beta levels until the pre-parturient rise which occurred earlier in twin pregnancies. Intra-muscular injection of progesterone had no measurable effect on peripheral plasma levels of estradiol-17beta in Charolais cows 31 - 32 weeks pregnant.     

In vitro-produced equine embryos: production of foals after transfer, assessment by differential staining and effect of medium calcium concentrations during culture

Viability of equine embryos produced by oocyte maturation, intracytoplasmic sperm injection and embryo culture to the blastocyst stage in vitro was evaluated after transfer of embryos to recipient mares. No pregnancies were produced after transfer of five blastocysts that had been cultured in G media. Transfer of 10 blastocysts cultured in modified DMEM/F-12 medium produced five pregnancies and three live foals; the two lost pregnancies developed only trophoblast (based on transrectal ultrasonography). To evaluate the status of the inner cell mass, equine blastocysts produced in vivo and in vitro were assessed after differential staining. A discrete inner cell mass could not be appreciated in blastocysts of either source after staining; this was attributed to the presence of a network of cells within the trophoblastic vesicle. Because increased medium calcium concentrations have been reported to decrease the incidence of trophoblast-only pregnancy after transfer of equine nuclear transfer embryos, we investigated the effect of increased calcium concentrations during oocyte maturation or during embryo culture. Increasing calcium concentration of culture medium from 2 to 5.6mM during in vitro oocyte maturation did not affect maturation rate (75 and 68%, respectively) or blastocyst development after fertilization (23 and 27%). However, increasing calcium concentration (from 1.3 to 4.9 mM) of medium used for embryo culture significantly decreased blastocyst development (27% versus 13%, respectively) and adversely affected embryo morphology. More work is needed to optimize culture systems for in vitro production of equine embryos.     

Comparative study of placental protein 19, human chorionic gonadotrophin and pregnancy-specific beta 1-glycoprotein as immunohistochemical markers for extravillous trophoblast in pregnancy and trophoblastic disease

PP19, a new placental tissue protein, has alpha 1-beta 1 electrophoretic mobility, a molecular weight of 36,500 and 3.9% carbohydrate. To study immunocytochemical PP19 localization in extravillous trophoblast, we obtained formalin-fixed specimens from extravillous tubal pregnancy at gestational weeks (GW) 7-9 (12 blocks); four early intrauterine pregnancies at GW 7-13 (12 blocks); four late pregnancies at GW 28-38 complicated with intramural uterine myoma, placenta increta and abruptio placenta (8 blocks); four invasive complete moles (9 blocks); and seven primary and metastatic gestational choriocarcinomas (12 blocks). Immunohistochemical staining was done for PP19, pregnancy-specific beta 1-glycoprotein (SP1) and human chorionic gonadotrophin (hCG) using the indirect-labeled antibody method [purified PP19 (Lot no. 225/242) and antibody against PP19 (Lot no. 632ZA) prepared by H. Bohn, antibodies against hCG (Behringwerke, Marburg, FRG) and SP1 (Dakopatts, Copenhagen, Denmark)]. In both early and late intrauterine pregnancies, the extravillous syncytiotrophoblastic cell (XST) showed positive staining for hCG and SP1 in the cytoplasm, as well as for PP19, which stained more intensively in the nucleus than in the cytoplasm. The three proteins were not seen in the evtravillous cytotrophoblastic cell (XCT) in the trophoblastic cell column and shell. The interstitial cytotrophoblast-like cell (ICT), which infiltrated into the decidua and myometrium, and their blood vessels, was immunoreactively positive for PP19 but negative for hCG and SP1 with the exception of SP1-positive ICT in the myometrium in late pregnancy. XST and ICT in the endosalpinx of tubal pregnancy stained for all three proteins.(ABSTRACT TRUNCATED AT 250 WORDS)