High pregnancy rates and successful prevention of severe ovarian hyperstimulation syndrome by 'prolonged coasting' of very hyperstimulated patients: a multicentre study.

In a multicentre trial, 65 in-vitro fertilization (IVF)-embryo transfer cycles were severely hyperstimulated. Instead of cancelling the cycle, gonadotrophins were withheld for a 'coasting period' until serum oestradiol concentrations had dropped below 10,000 pmol/l (mean 4.3 days), and then human chorionic gonadotrophin was administered. Four cycles were cancelled and there were 61 oocyte aspirations. A total of 103 fresh embryos was transferred to 53 patients, resulting in a pregnancy rate of 42% per started cycle (51% per embryo transfer), with an implantation rate of 31%. Only one patient developed severe ovarian hyperstimulation syndrome (OHSS). Four patients developed moderate OHSS. In all, two patients were hospitalized for OHSS. In order to optimize the coasting procedure, it seems important that each IVF centre identifies its appropriate cut-off limits for serum oestradiol concentrations and follicle size for initiating and ending of the coasting period. Correctly handled, it seems to be a major advance in the search for improved stimulation policies for high-responders.

First trimester live pregnancy and subsequent fetal loss. Impact of transcervical CVS and colonization of the cervix.

A consecutive series of 224 women undergoing transcervical chorionic villi sampling (CVS) were analyzed for the presence of cervical microbes. The outcome of pregnancy was related to age, number of aspirations and to the presence or not of microbes. The CVS group was compared to a group of 200 women with live fetuses at 8-11 weeks of gestation not undergoing CVS (ultrasound, US group). In the US group the miscarriage rate was 8.5% with 5.9% occurring after the 16th week of gestation. In the CVS group 20.3% ended as a miscarriage, 28.9% of these after the 16th week. There was no correlation between miscarriage rate and maternal age in the US group. In the CVS group younger women had a prominent rate of fetal loss. In the present study the risk of fetal loss after CVS was associated with a previous history of spontaneous abortions, with several aspirations performed, and with bacterial colonization of the cervix--candida and gardnerella excluded.

Information on prenatal diagnosis at the antenatal clinic. The women's experiences.

The issue of information and autonomy (informed consent) in prenatal diagnosis (PND) was studied by questionnaires given to women undergoing amniocentesis (group A, n = 122) or chorionic villus biopsy (group V, n = 90). About 1/4 of the women were also interviewed. Sixty-eight percent of the women had learnt most about PND already before visiting the antenatal clinic. More women in group A (75%) than in group V (51%) were satisfied with the information given at the clinic, probably because amniocentesis is a well-known routine, while chorionic villus biopsy is not. Further, in both groups, more of the women who underwent PND because of age were satisfied with the information than those having PND because of strong fear of giving birth to a handicapped baby. This might be explained by the complicated character of this fear, which the medical staff could not always understand and meet. Also the women who were investigated because of a known genetic problem seemed to need more specialized genetic counselling. Fifty-eight percent of the women were well informed about the risk of giving birth to a child with a congenital disorder and 83% about which disorders could be detected by the procedure they were undergoing. Seventy-three percent had not felt any uneasiness when they were offered PND by their midwife or gynecologist; 18% had initiated the discussion themselves. Seventy-four percent of the women recommended that the medical staff actively offered PND. Most women (87%) answered that the midwife's or gynecologist's attitude towards PND had been positive. The majority (85%) considered that there is a risk of persuasion in counselling.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome of pregnancy in relation to maternal serum alpha-fetoprotein levels in the second trimester. An evaluation of a screening program and a longitudinal follow-up.

120 women with elevated alpha-fetoprotein (AFP) in pregnancy week 16-17 were subsequently supervised every 4th week until a few days postpartum. A group of 102 women with normal (n = 78) or low (n = 24) serum AFP concentrations in pregnancy week 16-17 were studied in the same way. In the last week before parturition the AFP serum level declined and the decrease was more pronounced with increasing gestational duration up to pregnancy week 41. The AFP level relationship between the women was stable on average throughout the pregnancies. Smoking was found to be related to elevated maternal serum AFP levels in pregnancy week 16-17. Among mothers younger than 25 years, 72% of those with high or very high AFP serum levels in pregnancy week 16-17 were smokers. Among women with elevated or much elevated maternal serum AFP levels in pregnancy week 16-17, male fetuses predominated. But only those carrying female fetuses gave premature birth to small-for-date children. Further analysis of the data revealed that if such a woman was a multipara, there was a 54% risk of a small-for-date premature female baby. Other data indicate that this risk may be increased by smoking and maternal age. It is recommended that this category of mothers with elevated AFP in pregnancy week 16-17 is continuously supervised during pregnancy.

Effect of intraperitoneal instillation of 32% dextran 70 on postoperative adhesion formation after tubal surgery.

The intraperitoneal instillation of 32% dextran 70 (HyskonR, Pharmacia AB, Sweden) has previously been reported to prevent the formation of postoperative adhesions. Against this background, the present study was undertaken to evaluate the efficacy of HyskonR in counteracting peritoneal adhesions following tubal microsurgery. 105 infertile women were operated upon in a prospective, randomized, controlled, double-blind, multicenter study. The intra-abdominal adhesions present from the beginning were classified by means of a standardized scoring scale and the extent of adhesions was again evaluated at follow-up laparoscopy 4-10 weeks later. A reduction in the extent of the intra-abdominal adhesions (statistically highly significant) was revealed in both the Hyskon group and the saline control group. The extent of adhesions in the Hyskon group was not lesser than in the saline group, however. The pregnancy rates in the two groups were also similar.

The fast inhibitor of tissue plasminogen activator in plasma during pregnancy.

The novel fast inhibitor to tissue plasminogen activator in plasma has been determined in 20 healthy non-pregnant women, 48 apparently healthy pregnant women and 136 women with risk pregnancies (preeclampsia, suspected fetal growth retardation, thrombosis or previous history of thrombosis, diabetes and others). In healthy fertile non-pregnant women, the inhibitor concentration was found to be 0.4 +/- 0.7 U/ml. In pregnant women the concentration stayed at this level until week 10, but then an almost linear increase was found, reaching about 6.5 U/ml at week 40. In plasma samples from the patients with risk pregnancies many with deviating concentrations were found. Thus, in the last trimester a range of 0-24.0 U/ml was found in these patients, as compared to 4.0-6.4 U/ml in healthy pregnant women. The pathophysiological impact of this finding is at present unclear.

Prenatal diagnosis of chondroectodermal dysplasia with fetoscopy.

Chondroectodermal dysplasia (Ellis-van Creveld syndrome) has previously been diagnosed prenatally only once, using fetoscopy. We report on two consecutive pregnancies in a woman at risk of having a child with the syndrome during which fetoscopic visualization was performed. Ellis-van Creveld syndrome was diagnosed prenatally in one instance, while it could be excluded in the other one. Non-invasive prenatal diagnosis of the syndrome is discussed.

Smoking and sister chromatid exchange.

Smokers were shown to have significantly higher SCE levels in peripheral lymphocytes than non-smokers. The increase of SCE was found to depend on the cigarette consumption, and to be significantly higher in subjects with a long than with a short history of smoking. Analysis of the frequency distribution of individual SCE levels and of SCE numbers in single cells gave no indication of subgroups of individuals of subpopulations of lymphocytes with an increased SCE response to smoking. Cells from smokers cultivated in plasma from non-smokers retained a high SCE level, and cells from non-smokers cultivated in plasma from smokers no increase of SCE, indicating that the increase of SCE caused by smoking is due to some type of (long-lived) cellular damage rather than to serum factors. The plasma levels of the primary nicotine metabolite cotinine were found to be increased in heavy smokers as compared to light smokers, and showed an excellent correlation with the cotinine levels in the amniotic fluid in pregnant female smokers. No correlation was found between the individual SCE and cotinine levels in smokers, which indicates that the degree of exposure to SCE-inducing genotoxic agents in the cigarette smoke is not related to plasma cotinine levels in any simple way. The induction of DNA strand breaks and SCE by two intermediary benzo(a)pyrene (BP) metabolites was studied in human lymphocytes in vitro. Both 9-OH-BP and BP-7,8-dihydrodiol were found to induce DNA breaks, but only the latter compound induced SCE. The SCE-inducing effect of BP-7,8-dihydrodiol was observed at a very low concentration (0.01 microM), which indicates a possible role for this BP derivative in the smoking-induced increase of SCE in vivo.

Incidence of Down's syndrome in Sweden during the years 1968-1977.

The incidence of Down's syndrome has been studied among children born in Sweden during the years 1968-1977. The risk for mothers of different ages of bearing such a child did not change during these years. This does not exclude that a change in incidence might have occurred in smaller areas of the country but escaped detection for statistical reasons. A higher than expected number of children with Down's syndrome were born in a few communities, which most likely is a chance event. No correlation could be detected between the incidence of Down's syndrome and a number of socioeconomic variables. The correlation with maternal age was studied in detail. There was a significant excess of males among both the newborn children with Down's syndrome and fetuses with trisomy 21 aborted after prenatal diagnosis. A similar tendency was found among the cases with a chromosome mosaicism but not among those with a translocation. Two hypotheses are put forward to explain the excess of males with trisomy 21.

Teratology study in the mouse using a prostaglandin and a prostaglandin synthetase inhibitor.

Prostaglandin F2 alpha alone and in combination with sodium salicylate, was administered i.m. to pregnant CBA mice at various times on day 9 of gestation. A high frequency of rib malformations (90%) was recorded whereas the resorption rate was moderate (18%). When combining prostaglandin treatment (25 mg/kg i.m.) with sodium salicylate (500 mg/kg i.m.), the resorption rate increased. The malformation frequency remained unchanged except for the group with combined treatment at 10 a.m. (=maximum teratogenic period for salicylate induced rib malformations). This treatment resulted in a high frequency of maternal death; the resorption frequency was 75% and the surviving foetuses were malformed.

Effects of ethinylestradiol/D-norgestrel combinations on serum lipoproteins.

Serum lipoproteins were analyzed in 33 young women (mean age 22 years) before and after two cycles of treatment with one of the following ethinylestradiol/d-noirgestrel combinations (microgram/microgram): 30/150, 50/150 and 50/250. A slight but significant weight increase of 1.2 akg was found only in the 509/150 group. All three hormone combinations had similar effects on the lipoproteins. Before treatment all subjects had normal lipoprotein concentrations. Whole serum triglyceride (TG) and cholesterol concentrations were not significantly affected. In the whole group the LDL-TG concentration increased from 0.24 to 0.33 mmol/l (p < 0.001) and HDL-cholesterol fell from 1.54 to 1.35 mmol/l (p < 0.001). Smokers tended to have lower HDL-cholesterol than non-smokers. It is possible that HDL reductions for longer periods of time may be one of the factors that promote the development of atherosclerotic manifestations in young women on oral contraceptives.

[Oral contraceptives and HDL cholesterol]. / P-piller och HDL-kolesterol.

PIP: Serum lipid and cholesterol levels were measured in 33 women before and after 2 cycles' use of 3 low dosage combination preparations. Cholesterol levels in the HDL fraction showed a 12% decrease (P .001). Serum-TG and cholesterol levels in other fractions did not change significantly in any of the 3 groups.^ieng

Developmental precocity after asynchronous egg transfer in mice.

Asynchronously transferred ova were found to implant 6-8 h earlier than did non-transferred eggs, indicating that the endometrium was receptive to implantation several hours before the native blastocysts were prepared to implant. This developmental precocity was also preserved on day 14, according to the results of a morphological rating study on day 14. Synchronously transferred ova showed no such developmental precocity. No statistically significant difference in implantation time or development on day 14 was found between the two strains, CBA and A/Jax. The importance of precocious development for planning teratological studies is emphasized.

Agent-determined type of maternal influence on induced cleft palate in mice.

The maternal influence on induced cleft palate frequency, as revealed by reciprocal crosses, was investigated after treatment with triamcinolone or cortisone. Mouse blastocysts from the CBA and A/Jax strains were transferred to pseudopregnant A/Jax and CBA foster mothers and in addition CBA X A/Jax and A/Jax X CBA embryos were raised in pseudopregnant CBA foster mothers. According to the period of maximum sensitivity revealed by a time response study triamcinolone was injected as a single dose (2 mg/kg, i.m.) on day 11 at 8 a.m. when the precocious development of transferred fetuses had been taken into account. A predominant uterine factor slightly modified by the fetal genome was found. This was in contrast to the effect of the 4-day treatment with cortisone (62.5 mg/kg i.m.) where, as also previously has been shown, cytoplasmic factors in the embryos were accountable for the magnitude of the teratogenic response. An increased corticoid elimination from the resistant CBA fetuses might explain the maternal influence on triamcinolone treatment but would not be responsible for the influence on cortisone-induced cleft palate frequency.