Midtrimester N-terminal proatrial natriuretic peptide, free beta hCG, and alpha-fetoprotein in predicting preeclampsia.

OBJECTIVE: To determine whether maternal midtrimester serum N-terminal peptide of proatrial natriuretic peptide, free beta subunit of human chorionic gonadotropin (hCGbeta), or alpha-fetoprotein (AFP) levels can predict preeclampsia. METHODS: A population-based cohort included 1037 nulliparous women, of whom 637 (61%) participated in a maternal serum Down syndrome screening program. Measurements of hCGbeta, AFP, and N-terminal peptide of proatrial natriuretic peptide were made from maternal serum collected at 15-19 weeks' gestation. Sensitivity, specificity, and predictive values were calculated for elevated AFP (at least 2.0 multiples of the median [MoM]) and hCGbeta (at least 2.0 MoM) values. RESULTS: No difference was found in the concentrations of the N-terminal peptide of proatrial natriuretic peptide among the 30 women in whom preeclampsia developed later (median 270 [range 142-604] pmol/L) compared with 536 women who remained normotensive (274 [51-2626] pmol/L). The sensitivity and specificity of elevated AFP in predicting preeclampsia were 3% and 98% and those of elevated hCGbeta were 20% and 84%, respectively. When a stepwise multiple logistic regression model was used, only mean arterial pressure was an independent risk factor in predicting preeclampsia. CONCLUSION: Determinations of the proposed new marker N-terminal peptide of proatrial natriuretic peptide, as well as serum hCGbeta or AFP, are not helpful in predicting preeclampsia.

An increase of the plasma N-terminal peptide of proatrial natriuretic peptide in preeclampsia.

OBJECTIVE: To determine whether increased concentrations of the N-terminal peptide of proatrial natriuretic peptide and of atrial natriuretic peptide are related to the severity of preeclampsia and gestational hypertension. METHODS: Blood samples were collected from 70 healthy pregnant women, 48 women with preeclampsia, and 19 women with gestational hypertension in the third trimester. We used a specific radioimmunoassay (RIA) method suitable for the determination of the plasma N-terminal peptide of proatrial natriuretic peptide in unextracted plasma. The atrial natriuretic peptide was measured by RIA from Sep-Pak C18-extracted plasma. RESULTS: The N-terminal peptide of proatrial natriuretic peptide levels were significantly higher in preeclamptic women than in healthy pregnant controls (median 571 [range 189-2000] versus 266 pmol/L [80-634], P < .001) and also significantly higher in women with severe preeclampsia than in women with mild preeclampsia (766 [431-2000] versus 492 pmol/L [189-1283], P = .01). The N-terminal peptide of proatrial natriuretic peptide values were significantly elevated in the subgroup of hypertensive pregnancies with abnormal Doppler velocimetry. At entry into the study the values for the N-terminal peptide of proatrial natriuretic peptide were higher in the subgroup of women who developed severe preeclampsia and/or gave birth to a small for gestational age (SGA) infant compared to the values in the subgroup of women in whom the hypertensive condition remained stable (710 [271-1475] versus 407 pmol/L [189-1067], P = .006). Similar comparisons of atrial natriuretic peptide values did not reach significant differences. CONCLUSION: The levels of N-terminal peptide of proatrial natriuretic peptide were higher in women with preeclampsia than in those with gestational hypertension and higher in women with gestational hypertension than in those with normal pregnancies. A marked elevation in N-terminal peptide of proatrial natriuretic peptide may predict development of severe preeclampsia and/or an SGA infant.

Changes in maternal heart dimensions and plasma atrial natriuretic peptide levels in the early puerperium of normal and pre-eclamptic pregnancies.

OBJECTIVE: To measure plasma atrial natriuretic peptide (ANP) in relation to maternal haemodynamics and body fluid balance in the early puerperium following uncomplicated pregnancy and pre-eclampsia. DESIGN: A longitudinal study from late pregnancy and into the early postpartum period (days 1 to 3 and days 4 to 6) compared with nonpregnant controls. SUBJECTS: Eleven women with uncomplicated pregnancies, 12 women with pre-eclampsia and 12 healthy, nonpregnant women. MAIN OUTCOME MEASURES: Maternal heart dimensions determined by M-mode echocardiography, concentrations of ANP, and daily urine output and sodium excretion. RESULTS: After delivery increases in left atrial dimensions, represented as mean (SEM), from 33.2 (1.6) to 37.7 (1.7) mm and ANP levels from 7.9 (1.1) to 19.0 (2.7) pmol/L were observed at 1-3 days postpartum in normal pregnant women, but we were not able to demonstrate a significant increase in diuresis and natriuresis. In the third trimester left atrial dimensions (38.4 (1.2) mm) and ANP levels (15.4 (2.2) pmol/L) were greater in pre-eclampsia. ANP levels rose further in pre-eclamptic women in the early puerperium (27.4 (7.4) pmol/L) with an increase in diuresis and natriuresis, while left atrial dimensions did not change significantly (39.4 (1.7) mm). A pericardial effusion was found in 11 pre-eclamptic but in only three healthy pregnant women. CONCLUSIONS: A concommitant increase in left atrial dimensions and ANP in the early puerperium following uncomplicated pregnancies is consistent with the mechanism of atrial stretch as a stimulus for ANP release, although the biological significance of this finding remained unclear. A significantly higher release of ANP in the early puerperium after pregnancies complicated by pre-eclampsia may be a mechanism which promotes the renal elimination of excessive body fluids and sodium.

Obesity and endocrine disorders in women taking valproate for epilepsy.

We recently reported the frequent occurrence of polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy, especially when the medication was started before the age of 20 years. In the present study we evaluated the association of obesity and hyperinsulinemia with valproate-related polycystic ovaries and hyperandrogenism in women with epilepsy. Sixty-five women participated in the study. Twenty-two received valproate monotherapy and 43 received carbamazepine monotherapy. In addition to clinical examination, vaginal ultrasonography was performed to determine ovarian size, and the concentrations of serum sex hormones, insulin, insulin-like growth factor 1, and the insulin-like growth factor-binding proteins 1 and 3 (IGFBP-1 and IGFBP-3) were measured. Fifty-nine percent of the women on valproate were obese, and in a retrospective analysis an indisputable weight gain (mean, 21 kg; range, 8-49 kg) was found in 50% of the women taking valproate. Fourteen (64%) of the women on valproate had polycystic ovaries, hyperandrogenism, or both. These women were obese, and in addition to elevated serum androgen levels, they had high concentrations of fasting serum insulin and low levels of serum insulin-like growth factor-binding protein 1. Valproate therapy for epilepsy is associated with weight gain during treatment in approximately 50% of women patients. The weight gain can be progressive, and is associated with hyperinsulinemia and low serum levels of insulin-like growth factor-binding protein 1, which may lead to hyperandrogenism and polycystic ovaries.

Effect of intravenous fluid preload on vasoactive peptide secretion during Caesarean section under spinal anaesthesia.

The endogenous release of the vasoactive peptides atrial natriuretic peptide and endothelin-1 may modify maternal haemodynamic responses to a rapid intravenous volume load used to prevent hypotension at elective Caesarean delivery under spinal anaesthesia. Twenty-two healthy pregnant women were examined during elective Caesarean section at term pregnancy. They were randomly assigned to receive either 2000 ml of Ringer lactate solution (crystalloid group) or 500 ml of 6% hydroxyethyl starch + 1000 ml of Ringer lactate solution (colloid group). The mean (SEM) concentration of atrial natriuretic peptide in plasma increased from 10.9 (1.5) to 24.7 (5.1) pmol.l-1 during crystalloid infusion and from 10.3 (1.4) to 28.2 (5.6) pmol.l-1 during colloid infusion. A slight decrease in endothelin-1 levels was found during colloid infusion. A significant increase in the release of atrial natriuretic peptide in response to volume load may decrease vascular tone and initiate diuresis, thereby attenuating the effect of volume load on blood pressure during elective Caesarean delivery.

The expression of insulin-like growth factor and its binding protein mRNA in the endometrium of postmenopausal patients with breast cancer receiving tamoxifen.

BACKGROUND: Insulin-like growth factor I (IGF-I) is known to mediate estrogen effect in the uterus, whereas IGF binding proteins (IGFBPs) modulate the biologic effects of IGF-I. Tamoxifen may act via the IGF-IGFBP system in the postmenopausal endometrium. METHODS: Endometrial samples were collected from 16 postmenopausal women with breast cancer of whom 9 received tamoxifen and the remaining 7 received no hormonal treatment. The expression of messenger RNA for IGF-I, IGF-II, and the IGFBPs 1-6 was studied using dot blot and Northern blot techniques. RESULTS: Expression of mRNA for IGF-I, IGFBP-2, -3, -4, and -6 was present in endometrial specimens. The expression of IGF-I mRNA was similar in the tamoxifen-treated and control patients, whereas mRNA expression for IGF-II was not detected. The expression of IGFBP-2 and -4 mRNA predominated in the endometrium of patients who received tamoxifen. CONCLUSIONS: These findings demonstrate that the IGF-IGFBP system is present in the postmenopausal endometrium and may be modulated by tamoxifen.

Menstrual disorders in women with epilepsy receiving carbamazepine.

We measured concentrations of serum sex hormones and sex hormone binding globulin (SHBG) in relation to regularity of the menstrual cycles in 8 women before carbamazepine (CBZ) treatment was initiated and after 1 and 5 years of CBZ therapy. In addition, we evaluated menstrual cycle regularity and related endocrine changes in 56 women receiving CBZ treatment for > 5 years. Serum SHBG levels increased, and serum concentrations of 17 beta-estradiol (estradiol) and estradiol/SHBG ratio decreased during CBZ treatment. Two of the 8 patients (25%) in the prospective study group developed menstrual irregularities during the first 5 years of therapy. In the cross-sectional study group of patients treated with CBZ for > 5 years, the frequency of menstrual disturbances was also 25.0% (14 of 56 patients). Concentrations of serum sex hormones and SHBG were measured in 13 women with menstrual disorders and in 11 randomly selected women with regular cycles. In most cases, menstrual disorders were associated with increased serum SHBG and decreased serum estradiol levels and low estradiol/SHBG ratio. Long-term CBZ treatment results in increased serum SHBG levels and decreased estradiol effect, which correlate with the frequency of menstrual disorders in CBZ-treated women with epilepsy.

Serum lipids and lipoproteins in postmenopausal women receiving transdermal oestrogen in combination with a levonorgestrel-releasing intrauterine device.

OBJECTIVES: To compare the effects of a non-oral combination of a transdermal oestradiol patch (50 micrograms daily) and an intrauterine device (IUD) releasing 20 micrograms of levonorgestrel daily on the serum pattern of lipids and lipoproteins with an established oral regimen of a daily dose of 2 mg of estradiol and 1 mg of noretisterone acetate. METHODS: An open, randomized study comprised of 40 healthy, early postmenopausal women. RESULTS: During 1 year the concentration of total cholesterol decreased 5.0% in the LNg-IUD group and 10.6% in the oral therapy group; HDL cholesterol decreased 10.9% and 12.8%, respectively, and HDL2 cholesterol decreased 18.1% and 26.9%, respectively. LDL cholesterol values did not change in the LNg-IUD group, whereas a 10.3% decrease was observed in the oral therapy group. Triglyceride values did not change in either group. There were no significant differences in the serum lipoprotein changes between the groups during the treatment. CONCLUSIONS: The use of a non-oral regimen of hormone replacement therapy has been advocated to minimize the effect of steroids on the liver. Its effects on the serum pattern of lipids and lipoproteins, however, did not differ significantly from those induced by a continuous oral treatment regimen.

Transdermal estrogen with a levonorgestrel-releasing intrauterine device for climacteric complaints: clinical and endometrial responses.

OBJECTIVE: Our purpose was to study the effects of intrauterine release of a daily dose of 20 micrograms levonorgestrel by an intrauterine device on climacteric symptoms, bleeding pattern, and endometrial histologic features in postmenopausal women receiving transdermal estrogen replacement therapy. STUDY DESIGN: Forty parous postmenopausal women were randomly allocated into two groups for 1 year: 20 women receiving a continuous transdermal daily dose of 50 micrograms of estradiol had a levonorgestrel-releasing intrauterine contraceptive device inserted, and the control group of 20 women received a continuous oral dose of 2 mg of estradiol valerate and 1 mg of norethisterone acetate daily. The climacteric symptoms, bleeding patterns, endometrial thickness, and endometrial changes in biopsy samples were analyzed. Serum levels of estradiol in both groups and levonorgestrel levels in the intrauterine device group were also determined. RESULTS: Both treatment regimens effectively relieved climacteric symptoms. Spotting was more common in the intrauterine contraceptive device group than in the oral therapy group for the first 3 months. After that, the proportion of women without any bleeding was similar in both groups. Two patients in each group dropped out because of bleeding. CONCLUSION: These preliminary findings suggest that the levonorgestrel-releasing intrauterine contraceptive device is a useful alternative mode of progestin administration for certain selected women receiving estrogen replacement therapy.

PIP: The purpose was to study the effects of intrauterine release of a daily dose of 20 mcg levonorgestrel by an IUD on climacteric symptoms, bleeding pattern, and endometrial histologic features in postmenopausal women receiving transdermal estrogen replacement therapy. 40 parous postmenopausal women were randomly allocated into 2 groups for 1 year. They were required to be parous, to have an intact uterus, and to have had amenorrhea for at least 6 months but less than 5 years. 20 women received a combination of 50 mcg of estradiol per 24 hours delivered transdermally from a patch, and received estrogen pretreatment for 1 month to make insertion of a levonorgestrel-releasing IUD (Levonova), which was installed a month later, easier. This combination was continued for 1 year. The control group of 20 women received an established form of continuous oral estrogen and progestin with a daily dose of 2 mg of estradiol, and 1 mg of norethindrone acetate also administered for 1 year. Checkup visits were scheduled at 3, 6, and 12 months. The climacteric symptoms, bleeding patterns, endometrial thickness, and endometrial changes in biopsy samples were analyzed. The increase in estradiol concentration was similar in both groups, and the mean concentrations of levonorgestrel in the IUD group were 216 +or- 25 pg/ml at 3 months, 209 +or- 11 pg/ml at 6 months, and 212 + 10.5 pg/ml at 12 months. Both treatment regimens effectively relieved climacteric symptoms. The IUD group experienced more days of bleeding, primarily spotting, during the first 3 months than did the oral therapy group but the differences between the groups had disappeared by 6 months. Both treatments resulted in an atrophic endometrium developing from a proliferative one. Two patients in each group dropped out because of bleeding. The levonorgestrel-releasing IUD is a useful alternative mode of progestin administration for certain selected women receiving estrogen replacement therapy.

Plasma insulin-like growth factor I and its binding proteins 1 and 3 in postmenopausal patients with breast cancer receiving long term tamoxifen.

BACKGROUND: Insulin-like growth factor I (IGF-I) is a potent mitogen for breast cancer cells. The majority of IGF-I in plasma is bound to IGF binding proteins (IGFBPs), which modulate the biologic effects of IGF-I. METHODS: Plasma concentrations of IGF-I, IGFBP-I, and IGFBP-3 were compared between 40 postmenopausal breast cancer patients receiving long term tamoxifen therapy and 39 breast cancer patients receiving no hormonal treatment. In an additional group of seven patients, serum levels of IGF-I and IGFBP-1 were determined before and during treatment at 6 and 12 months. RESULTS: The tamoxifen and the control groups did not differ with respect to age, parity, age at menopause, or body mass index. There were no significant differences in the mean concentrations (+/- standard error of the mean) of IGF-I (10.0 +/- 0.4 nmol/l and 11.2 +/- 0.5 nmol/l, respectively) and IGFBP-3 (3.2 +/- 0.1 mg/l and 3.1 +/- 0.1 mg/l, respectively), whereas the mean value of IGFBP-1 was significantly higher in the tamoxifen group (6.0 +/- 0.6 micrograms/l versus 2.8 +/- 0.3 micrograms/L, P = 0.0001). No significant differences were found in the insulin levels. During the treatment, concentrations of IGF-I decreased at 6 months and began increasing at 12 months. IGFBP-1 levels increased at 6 months and remained elevated at 12 months. CONCLUSIONS: The tamoxifen-induced increase in IGFBP-1 plasma levels may be an important mechanism modulating IGF-I action at the tissue level.

Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy.

BACKGROUND: Reproductive endocrine disorders are more common among women with epilepsy than among normal women. These disorders have been attributed to epilepsy itself, but could be related to antiepileptic-drug therapy. METHODS: We studied 238 women with epilepsy who were seen regularly at the Outpatient Department of the University Hospital, Oulu, Finland. Their mean age was 33 years (range, 18 to 45), and the mean duration of therapy was 9 years (range, 0 to 31). Twenty-nine (12 percent) were treated with valproate, 120 (50 percent) with carbamazepine, 12 (5 percent) with valproate and carbamazepine, and 62 (26 percent) with other medications; 15 (6 percent) were untreated. Vaginal ultrasonography was performed to determine ovarian size, and serum sex-hormone concentrations were measured in 41 women with epilepsy and menstrual disturbances, 57 women with epilepsy and regular menstrual cycles, and 51 normal women. RESULTS: Menstrual disturbances were present in 13 of the women receiving valproate alone (45 percent), 3 of the women receiving valproate in combination with carbamazepine (25 percent), 23 of the women receiving carbamazepine (19 percent), and 8 of those receiving other medications (13 percent). Forty-three percent of the women receiving valproate had polycystic ovaries, and 17 percent had elevated serum testosterone concentrations without polycystic ovaries; 50 percent of the women receiving valproate and carbamazepine had polycystic ovaries, and 38 percent had elevated serum testosterone concentrations without polycystic ovaries. Eighty percent of the women treated with valproate before the age of 20 years had polycystic ovaries of hyperandrogenism. CONCLUSIONS: Menstrual disturbances, polycystic ovaries, and hyperandrogenism are often encountered in women taking valproate for epilepsy.

Serum levels of insulin-like growth factor binding protein-1 and ovulatory responses to clomiphene citrate in women with polycystic ovarian disease.

OBJECTIVE: To study the serum levels of insulin, insulin-like growth factor I (IGF-I), and insulin-like growth factor binding protein-1 (IGFBP-1) in relation to clomiphene citrate (CC) responsiveness in women with polycystic ovarian disease (PCOD). DESIGN: Prospective. PATIENTS, SETTING: Twenty-three women with PCOD admitted consecutively to the University Infertility Clinic, a tertiary referral center. INTERVENTIONS: Blood samples were taken at fasting state and during oral glucose tolerance test (OGTT) for the determination of insulin, IGF-I, and IGFBP-1. A dose of 50 to 200 mg/d CC was given for ovulation induction. RESULTS: With CC treatment, ovulation was achieved in 13 of 23 PCOD patients. The IGFBP-1 concentration was lower in CC nonresponders than in CC responders (20.5 +/- 4.0 ng/mL versus 41.0 +/- 8.5 ng/mL) (P < 0.05). This difference was accentuated in 13 lean PCOD patients. Lean CC nonresponders (n = 7) had almost threefold lower serum IGFBP-1 levels than lean CC responders (n = 6) (24.0 +/- 3.1 ng/mL versus 61.8 +/- 8.6 ng/mL) (P < 0.01). By contrast, among 10 obese PCOD patients, the IGFBP-1 levels were low irrespective of CC responsiveness (14.8 +/- 8.0 ng/mL versus 16.7 +/- 7.2 ng/mL). The differences remained during OGTT. The concentrations of IGF-I, insulin, sex hormone-binding globulin, LH, FSH, and androgens showed no significant differences between CC responders and nonresponders. There was an inverse correlation between serum insulin and IGFBP-1 levels in obese PCOD patients, whereas this was not seen in lean patients. CONCLUSION: In lean PCOD patients, low serum IGFBP-1 concentration is related to CC unresponsiveness by a mechanism unrelated to insulin.

Endothelin in maternal and umbilical cord blood in spontaneous labor and at elective cesarean delivery.

We measured endothelin-1, a potent vasoconstrictor peptide released by the vascular endothelium, in maternal, umbilical cord, and retroplacental blood plasma in cases of spontaneous and elective cesarean delivery. Mean (+/- standard error) endothelin-1 in the maternal plasma increased with advancing pregnancy, from 1.2 +/- 0.13 pmol/L at 32-34 weeks to 2.4 +/- 0.2 pmol/L at 38-41 weeks (P less than .01) and 3.4 +/- 0.3 pmol/L (P less than .02) during labor. Concentrations were significantly higher in umbilical cord plasma than in maternal venous plasma, and higher in the cord venous plasma after vaginal delivery (52.9 +/- 11.4 pmol/L) than after cesarean performed before the onset of labor (9.0 +/- 1.1 pmol/L) (P less than .001). In spontaneous labor, concentrations in the retroplacental blood plasma (23.3 +/- 4.5 pmol/L) were approximately ten times higher than those in the maternal peripheral blood. Levels in the umbilical cord and retroplacental blood plasma were the highest found so far in any physiologic condition, suggesting that an increased intrauterine release of endothelin-1 at delivery may promote constriction of the blood vessels in the umbilical cord and placental bed.

Corticotropin-releasing hormone and opioid peptides in reproduction and stress.

Increased knowledge on the mechanisms whereby corticotropin releasing hormone (CRH) and opioid peptides mediate the effects of stress has helped us to understand the relationship between stress and disturbed reproductive function. Increases of CRH and beta-endorphin in the hypothalamus in stressful situations inhibits the secretion of gonadotropins, oxytocin and vasopressin. This may lead to amenorrhea, which often is a consequence of intensive training or psychological stress, or it may disrupt parturition and lactation. There is a relationship between ovarian function and opioid peptides in the hypothalamus. Opioid peptides increase during puberty and fall at the menopause. Oestradiol and progesterone increase beta-endorphin concentrations in the luteal phase of the menstrual cycle, and this is followed by a rapid fall at menstruation. These changes may mediate symptoms typical of the premenstrual syndrome. Rather intensive exercise is required to increase plasma concentrations of beta-endorphin and corticotropin. During labour the amounts of beta-endorphin and corticotropin reach the values found in athletes during maximal exercise. The placenta produces increasing amounts of CRH towards the end of pregnancy which may help the mother and fetus to withstand the increased demands of labour. The placenta may thus be involved in the adaptation of the stress mechanism during pregnancy. CRH has also a paracrine function in different biological processes of the placenta and fetal membranes. It is possible to counteract the deleterious effects of stress on reproductive function by the administration of opiate antagonists. Induction of ovulation with naltrexone has been shown in patients with hypothalamic amenorrhea but the effect on fertility is not known.

Response of plasma beta-endorphin and insulin to oral glucose tolerance test in non-obese women with polycystic ovaries.

Increased responses of plasma insulin and endorphins to the oral glucose tolerance test (oGTT) have earlier been found in obese women. We studied responses of immunoreactive beta-endorphin (ir beta-E) and insulin in plasma to the oGTT in 8 non-obese women with polycystic ovaries (PCO) and in 10 healthy women. An additional control group consisted of 5 healthy women who were fasting during the study period. In the PCO group the insulin and glucose responses to the oGTT were increased, and an increase of ir beta-E from 5.9 +/- 1.5 to 8.6 +/- 2.8 pmol/l was found during the 1st half-hour period of the oGTT. In contrast, no significant change was found during the oGTT in healthy women (3.2 +/- 0.5 and 2.7 +/- 0.65 pmol/l, respectively), and in the fasting control women the mean ir beta-E level (+/- SE) decreased, from 4.5 +/- 1.2 to 3.6 +/- 1.1 pmol/l. These findings revealed increased responses of both plasma ir beta-E and insulin to the oGTT in non-obese women with PCO but their possible causal relationship remained unsolved.

Corticotropin-releasing hormone in amniotic fluid during gestation and labor and in relation to fetal lung maturation.

Corticotropin-releasing hormone was discovered in the placenta, and its concentration in the maternal plasma was found to increase greatly during the latter half of pregnancy. We studied the concentration of immunoreactive corticotropin-releasing hormone in amniotic fluid in 59 uncomplicated and in 73 complicated pregnancies. The mean (+/- SE) value of corticotropin-releasing hormone in amniotic fluid in uncomplicated pregnancies was significantly higher in the third (24.1 +/- 3.3 pmol/L) than in the second (9.1 +/- 0.7 pmol/L) trimester, but no change was found during labor. In groups matched by gestational age, larger mean values of corticotropin-releasing hormone and cortisol were observed in the group in which the lecithin/sphingomyelin ratio was greater than 2 or the phosphatidylglycerol test was positive than in the group with a lecithin/sphingomyelin ratio less than 2 or a negative phosphatidylglycerol test result. In samples taken at an interval of 1 to 3 weeks, concomitant increases in corticotropin-releasing hormone and cortisol levels were found with the appearance of phosphatidylglycerol. Concentrations of corticotropin-releasing hormone in amniotic fluid were elevated in patients with diabetes and in women with preeclampsia and intrauterine growth retardation. We conclude that the intrauterine release of corticotropin-releasing hormone increases during the last trimester. This may stimulate the fetal pituitary-adrenal axis and promote fetal maturation.

Factors influencing the success of microsurgery for distal tubal occlusion.

Ninety-three infertile women with distal tubal occlusion were subjected to salpingostomy in 1982-1984. In 78 of them follow-up data were available for 2-5 years. Second look laparoscopy was performed in 47 patients at a median of 4 months postoperatively. It showed one or both tubes patent in 45 (96%). In the total series of 93 patients, 13% had live births, 7.5% spontaneous abortions, and 13% ectopic pregnancies. Severe adnexal adhesions and the extent of fimbrial damage found at operation or at second look laparoscopy were the most significant factors related to the poor outcome of microsurgery. Our experience suggests that cases with severe adhesions and poor tubal status should be primarily directed to in vitro fertilization program rather than to microsurgery.