Modified natural cycle IVF (mnc-IVF) or mild IVF (m-IVF) was offered to selected patients between 1996 and 2007; 43 patients during 129 cycles were treated with mnc-IVF and 145 couples during 250 cycles were treated with m-IVF. Comparison with outcome from conventional IVF cycles during the same time period and in the same clinic was performed. Although 53.5 and 39.6% of started cycles respectively never reached embryo transfer, the ongoing pregnancy rates per embryo transfer were 26.7% for mnc-IVF and 27.2% for m-IVF. During the same time period, cancellation rate for conventional IVF was 13.7% and the ongoing pregnancy rate per embryo transfer was 34.3%. For patients > or =38years of age, the ongoing pregnancy rate per embryo transfer was 17.5% in the m-IVF group. None of the patients aged > or =38years in the mnc-IVF group achieved an ongoing pregnancy. For patients treated with conventional IVF, the > or =38years of age pregnancy rate per embryo transfer was 27.0%. Costs of medication for m-IVF and mnc-IVF were 96.3 and 97.5% less than for the least expensive conventional IVF cycle respectively. Pregnancy rates per embryo transfer are acceptable for these treatment modalities, the cost for medication is low, risks for complications are dramatically reduced, and the treatments may be more psychologically acceptable to the patients.

Three metabolites of 1,3-butadiene, namely butadiene diolepoxide, butadiene monoepoxide and diepoxybutane, were tested in the bacterial mutation assay using Salmonella typhimurium strain TA100 with and without metabolic activation (S9 mix). All three compounds showed a mutagenic response. The bifunctional epoxide was more effective than the diolepoxide which was more effective than the monoepoxide. Toxicity appeared to follow the ranking of the chemicals for their mutagenic potency. The monoepoxide and the diolepoxide were also tested for induction of micronuclei in mouse bone marrow erythrocytes and for dominant lethal mutation induction in postmeiotic male mouse germ cells. The effects of the diepoxide in both in vivo tests have been published earlier. In the micronucleus assay, the three metabolites gave a positive response whereby the diepoxide was more effective than the monoepoxide which was more effective than the diolepoxide. In contrast to the diepoxide which was positive at a dose as low as 36 mg/kg, the monoepoxide and the diol did not show an induction of dominant lethal effects up to doses of 120 and 240 mg/kg, respectively. It is concluded that the metabolites were mutagenic in bacteria without metabolic activation and clastogenic in mouse bone marrow; only the bifunctional diepoxide, however, was active in postmeiotic male mouse germ cells.

Benzene is a well-characterized human carcinogen and clastogen still present in both the occupational and general environment. However, the levels of benzene encountered today are, in most cases, relatively low and new methods, more specific and sensitive than classical cytogenetics, are probably needed to assess if current benzene exposures pose a genotoxic risk to human health. Bearing in mind the leukaemogenic action of benzene, blood lymphocytes appear to be a suitable cell system for biomonitoring studies. Buccal epithelium is an alternative source of tissue for monitoring human exposure to inhaled occupational and environmental genotoxicants. New molecular cytogenetic techniques allowing us to specifically study clastogenic or aneugenic events in human cells may provide the additional sensitivity required. In the present study, fluorescence in situ hybridization was used to examine the content of micronuclei (MN) (using the pan-centromeric DNA probe SO-alphaAllCen) in lymphocytes and buccal cells and to detect numerical abnormalities of chromosome 9 (using a chromosome 9 centromere-specific alphoid DNA probe) in buccal cells from a population occupationally exposed to benzene in an Estonian petrochemical plant. Age-matched Estonian volunteers were used as a control group. Individual benzene exposure levels were estimated to be around 1 p.p.m. (8 h time-weighted average). No increases in the frequency of total MN, MN harbouring whole chromosomes or acentric chromosomal fragments or chromosome 9 numerical abnormalities were detected in relation to benzene exposure in the present study. The lack of positive results was consistent in both buccal cells and lymphocytes, indicating that the benzene exposure levels encountered did not induce detectable clastogenic or aneugenic effects in the exposed workers. Other variables and confounding factors, such as age, smoking or alcohol consumption, did not influence any of the multiple cytogenetic biomarkers analysed.

Background. Our aims were to elucidate whether a decreased fertility in smoking women treated by in vitro fertilization (IVF) could be related to a divergent hormonal response to the controlled stimulation prior to IVF, to study the effect of smoking on the ovarian endocrine milieu and to possibly identify factors that might be detrimental to oocyte fertilization.Methods. Serum and follicular fluid concentrations of estradiol‐17β (E2), progesterone (P), testosterone (T), 4‐androstene‐3,17‐dione (A‐4), dehydroepiandrosterone (DHA), DHA sulfate (DHAS), sex hormone‐binding globulin (SHBG) and serum Cortisol were studied in 50 non‐smoking and 50 smoking women in an IVF program. Follicular fluid concentrations were also compared in follicles which gave rise to cleaved oocytes (TYPE I) and follicles which failed to yield fertilized oocytes (TYPE II) in the same woman.Results. The fertilization rate did not differ significantly between the two groups, but the live birth rate was 30% in non‐smokers and 4% in smokers. During treatment, serum A‐4, DHAS and the T/SHBG‐ratio were significantly higher in smokers than in non‐smokers. In the TYPE I follicles, smokers had higher follicular fluid concentrations of A‐4 and DHA and a higher E2/P ratio. The TYPE II follicles in smokers had higher A‐4 and T and lower E2 levels.Conclusions. Smoking women have a relative hyperandrogenism of ovarian origin, which may contribute to the lower pregnancy rate at IVF in this group.

Objective: The aim of this study was to compare insulin-treated, pregnant, diabetic patients with healthy pregnant women with respect to the effects of acute volume expansion on fete-maternal circulation, atrial natriuretic peptide (ANP), and its secondary messenger cyclic guanosine monophosphate (cGMP). Methods: Maternal venous blood was sampled and echocardiographic and Doppler investigations were performed before and after a 30-min infusion of a crystalloid solution (15 ml/kg). Results: Basal concentrations of ANP and cGMP were significantly higher in the patients than the controls (P < 0.01). In response to volume load, the ANP concentration, cardiac output, stroke volume, and systemic vascular resistance remained unaffected in the patient group in contrast to the healthy controls. The increase in cGMP was similar and the pulsatility index (PI) of the uterine and umbilical arteries remained unaffected in both groups. Conclusion: ANP and central circulatory responses were blunted during volume expansion in diabetic compared with normal pregnancy. However, the PI of the uterine and umbilical arteries was unchanged in both groups, indicating satisfactory blood flow regulation of these vascular beds during volume load.

OBJECTIVE:To compare normal pregnancy with pregnancy-induced hypertension (PIH)/preeclampsia with respect to the effects of acute volume expansion on plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP) and fetal-maternal circulation.DESIGN:Observational study.SETTING:University hospital.SUBJECTS:Fifteen women with PIH/preeclampsia and 15 healthy pregnant controls.INTERVENTIONS:Before and after 30 minutes' infusion of a crystalloid solution (15 ml/kg), maternal venous blood was sampled for ANP and cGMP analysis and echocardiographic and Doppler investigations were performed.RESULTS:Basal median (range) ANP and cGMP levels were significantly higher in the PIH/preeclampsia group compared to the controls: 6.5 (3.8-30.4) compared to 3.9 (2.0-6.7) pmol/l, p < 0.01 and 5.8 (2.4-11.6) compared to 4.0 (2.3-10.8) nmol/l, p < 0.05. The response to volume load was enhanced: 4.6 (-4.5-21.8) compared to 0.7 (-4.1-8.8), p < 0.05 and 2.9 (0.1-10.9) compared to 1.2 (-5.0-6.0), p < 0.05, respectively. Systemic vascular resistance was initially higher in the patient group, 22.3 (14.1-36.7) compared to 15.6 (10.0-25.5) peripheral resistance units, p < 0.01 but the response to volume load was similar in both groups (12-13% decrease). The pulsatility index of the uterine artery, 0.85 (0.46-1.38) compared to 0.72 (0.49-1.26) and umbilical artery 0.89 (0.66-1.57) compared to 0.97 (0.74-1.31) did not differ between the groups. Volume expansion did not affect any of these variables.CONCLUSIONS:The pulsatility index of the uterine artery remained unaffected in both preeclamptic patients and healthy controls despite an increase of ANP and cGMP concentration and a systemic vasodilatation during acute volume expansion. This finding may indicate the absence of a vasodilation of the uteroplacental vascular bed.

Infertility due to spinal cord injury (SCI) in males has been identified for decades as an area of major concern and techniques for assisted ejaculation are available. There has not been an overall consensus regarding which type of assisted procreation is the most appropriate for these couples. We describe here our experience from a programme based on assisted ejaculation combined with in vitro fertilization (IVF). Twelve couples have been treated so far and altogether 22 cycles with ovum pick-up have been completed. Fertilisation of the oocytes was obtained in 18 of these cycles. The overall oocyte fertilisation rate was 49%. Embryo transfer took place in 17 cycles, leading to seven clinical pregnancies. Four of the pregnancies are delivered or are ongoing, whereas three ended in first trimester spontaneous abortion. Thus our initial experience suggests that assisted ejaculation in combination with IVF is an effective option for these couples.

Strict blood glucose control of pregnant women with insulin-dependent diabetes is associated with increased risk of hypoglycemia. The hormonal and circulatory responses to an acute episode of insulin-induced hypoglycemia were studied in eight pregestational and one gestational diabetic women during the last trimester of pregnancy and 8 to 12 weeks postpartum. Following an overnight fast, insulin was injected intravenously (0.1 to 0.2 IU insulin/kg). Blood samples were taken at -15, 0, 15, 30, 40, 60, 90, and 120 minutes for analyses of metabolites (glucose, nonesterified fatty acid (NEFA), glycerol, 3-hydroxybutyrate) and counterregulatory hormones (epinephrine, norepinephrine, glucagon, and cortisol). Placental scintigraphy (indium-113m) was performed in five pregnant patients before and during hypoglycemia. Both during pregnancy and postpartum, blood glucose decreased to the same low level (3.2 mmol/L) concomitantly with significant decreases in NEFA, glycerol, and 3-hydroxybutyrate. Epinephrine and norepinephrine showed significant and similar increases on both occasions in relation to hypoglycemia, although there was no response in glucagon and cortisol concentrations. Maternal heart rate was significantly higher in the pregnant compared with the nonpregnant state and increased significantly in both groups in response to hypoglycemia. Placental blood flow showed no consistent changes and was unrelated to the glucose and catecholamine responses. Fetal heart rate remained unchanged. Thus, it seems as if hormonal and circulatory responses to acute hypoglycemia are not altered in diabetic women during pregnancy.

OBJECTIVE:To study the effects of low doses of the hormone atrial natriuretic peptide (ANP) on uteroplacental blood flow in patients with preeclampsia.METHODS:Eleven women with preeclampsia were infused intravenously with ANP (10 ng/kg/minute). Uteroplacental blood flow index was measured using dynamic placental scintigraphy with indium-113m. Regional blood flows were assessed by pulsed Doppler ultrasound and expressed as pulsatility index (PI). Hemodynamic measurements and blood sampling for peripheral venous plasma analysis of cyclic guanosine monophosphate (cGMP), an ANP second messenger, were performed before and after 30 minutes of infusion. Nonparametric statistics were used.RESULTS:The uteroplacental blood flow index increased by 28% (-2 to 58%; mean and 95% confidence interval). The Doppler findings were unaffected. Mean arterial blood pressure decreased from 112 (108-117) to 108 (103-114) mmHg (P < .01). Cyclic GMP increased significantly from 9.2 (6.2-12.3) to 17.4 (12.3-22.6) nmol/L (P < .01). Subjects exhibiting a substantial increase in uteroplacental blood flow index (25% or more) demonstrated a significantly greater cGMP response (P < .01) than those who did not (6% or less increase).CONCLUSION:A tendency to an increased uteroplacental blood flow index combined with minor blood pressure reduction after ANP infusion suggest the possibility of uteroplacental vasodilatation.

The genotoxicity of spent liquors from kraft softwood and hardwood pulp bleaching processes was studied using the Ames Salmonella test and the SOS chromotest. The induction of micronuclei, in vivo, was assayed in bone marrow erythrocytes of B6 mice treated with softwood first chlorination stage spent liquor. The softwood bleaching process used a combination of Cl-2 and ClO2 at the first chlorination stage. During the study the amount of free chlorine at the first chlorination stage in the softwood bleachery was gradually decreased, although the amount of active chlorine remained the same. Enzymatic bleaching was also used in a softwood process together with chlorine (Cl-2 + ClO2). The hardwood bleaching plant used only ClO2 at the first chlorination stage. A decrease in genotoxicity, corresponding to the decrease in Cl-2, was observed in the Ames Salmonella assays of the softwood bleaching plant effluents. A similar decrease was observed in the SOS chromotest. The highest decrease in mutagenic activity was observed when enzymatic bleaching was used together with chlorine.

[Electroejaculation and fertilization in vitro. A method used in infertility due to spinal injury].

We examined the genotypes of two polymorphic genes involved in the detoxification of several mutagenic and carcinogenic compounds in relation to tobacco smoking-associated urinary mutagenicity. The genes studied were the glutathione S-transferase-encoding GSTM1 gene and acetyltransferase-encoding NAT2 gene. Smokers with no GSTM1 gene (n = 7) had urine that was several times more mutagenic than that of smokers with the gene (n = 10). The mean level of urinary mutagenicity in presence of metabolic activation was 2527 +/- 958 revertants/100 ml urine for GSTM1-smokers compared to 766 +/- 560 revertants/100 ml for GSTM1+ smokers (P < 0.001) using the bacterial strain YG1024. The corresponding values using the TA98 strain were 336 +/- 124 and 123 +/- 75 (P < 0.001). In contrast, we failed to show any difference in the level of urinary mutagenicity between slow-acetylator and fast-acetylator NAT2 genotypes among smokers (n = 17) or non-smokers (n = 35). Our results offer one explanation for the recent findings that GSTM1 polymorphism is a risk modifier in smoking-related cancers, especially bladder cancer.

Acta Obstetricia et Gynecologica ScandinavicaVolume 73, Issue 8 p. 605-606 The ovarian hyperstimulation syndrome Still a clinical problem Lars Nylund M.D., PhD, Corresponding Author Lars Nylund M.D., PhDIVF-UNIT Sophiahemmet Hospital Valhallavägen 91, S-114 27, Stockholm, SwedenSearch for more papers by this authorKjell Carlström, Kjell CarlströmSearch for more papers by this authorOwe Gustafson, Owe GustafsonSearch for more papers by this author Lars Nylund M.D., PhD, Corresponding Author Lars Nylund M.D., PhDIVF-UNIT Sophiahemmet Hospital Valhallavägen 91, S-114 27, Stockholm, SwedenSearch for more papers by this authorKjell Carlström, Kjell CarlströmSearch for more papers by this authorOwe Gustafson, Owe GustafsonSearch for more papers by this author First published: September 1994 https://doi.org/10.3109/00016349409013451Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume73, Issue8September 1994Pages 605-606 RelatedInformation

Objective: The purpose of the investigation was to study the effects of the vasodilatory and antihypertensive drug dihydralazine on blood pressure, regional blood flows, and plasma concentration of atrial natriuretic peptide (ANP). Method: Fourteen women with severe preeclampsia in the third trimester of pregnancy were given 6.25 or 12.5 mg dihydralazine intravenously. Hemodynamic measurements by pulsed Doppler ultrasound were performed before and 30 min after the injection. During the same time interval, maternal venous blood was sampled for analyzes of ANP with radioimmunoassay. Results: The mean arterial blood pressure decreased significantly whereas the pulsatility index in the uterine artery increased. The pulsatility index of the umbilical artery and the maternal ANP concentration remained unaffected. Conclusions: These findings would imply an increased resistance in the uteroplacental circulation when the blood pressure is acutely reduced with dihydralazine treatment. The lack of reduction in circulating ANP levels does not corroborate the hypothesis that the elevated concentrations of ANP found in preeclamptic patients are secondary to vasoconstriction and increased blood pressure.

Cotinine concentrations in amniotic fluid samples from 22 smoking and 37 non-smoking pregnant women and induction of sister-chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells by samples from 15 smokers and 15 non-smokers were studied as indicators of exposure to potential genotoxic activity during pregnancy. Analysis of cotinine revealed one individual in the non-smoking group with a high cotinine level apparently due to non-reported smoking. The mean cotinine concentration of smokers was 85 ng/ml whereas non-smokers had a concentration of 0.3 ng/ml. According to interview data 16 persons announced some passive exposure to tobacco smoke at home or at work; however this group did not differ from unexposed non-smokers in their amniotic fluid cotinine concentration. SCE inducing activity was tested with and without metabolic activation. The mean SCE frequency in CHO cells induced in the presence of exogenous metabolic activation by concentrated amniotic fluid of heavy smokers (> or = 10 cigarettes/day) was significantly higher (9.7 +/- 0.6 SCE/cell) than among non-smokers (8.9 +/- 0.6 SCE/cell) with metabolic activation. The results show that amniotic fluid cotinine measurements and induction of SCEs in CHO cells can be used to indicate fetal exposure by maternal smoking and support earlier studies suggesting a potential genotoxic hazard to the fetus of heavy smokers.

Soxhlet-extracted samples of standard reference materials (SRMs) 1649 (PAR1: urban dust/organics) and 1650 (PAR2: diesel particulate matter) from the U.S. Institute of Standards and Technology were tested for induction of SOS functions using a semi-automated version of the SOS chromotest with Escherichia coli PQ37. Concentrations of 10 polycyclic aromatic hydrocarbons in the extracts were determined using reversed-phase HPLC. Only the diesel particulate matter (PAR2) extracts expressed SOS induction activity, which decreased when metabolic activation was used. Mutagenic PAH compounds (e.g., chrysene) were found in higher concentrations in the PAR2 extracts than in the PAR1 extracts but this could not explain the genotoxicity while it was mainly exhibited without metabolic activation. The direct genotoxic activity of the diesel particulate matter sample PAR2 is probably caused by nitroaromatic compounds; this was also supported by parallel studies with the Ames/Salmonella assay.

The effect of the calcium channel blocker, isradipine, on blood pressure and on uteroplacental and fetal blood flow was investigated in 27 patients with hypertension in pregnancy, before and after one week's treatment with 2.5 - 5.0 mg b.i.d. of the drug. In addition 21 hypertensive pregnant women without pharmacological treatment were investigated twice with a one week interval with regard to the same hemodynamic variables. Uteroplacental blood flow was investigated with dynamic placental scintigraphy. The uterine artery, the umbilical artery and fetal thoracic aortic blood flow velocity was measured by spectral doppler ultrasound. In the untreated group the blood pressure remained constant, and there were neither any changes in the uteroplacental or fetal blood flow variables. In the isradipine group there was a significant reduction in mean arterial blood pressure from 117 mmHg to 112 mmHg (p<0.001). Treatment with isradipine did not affect the uteroplacental blood flow or the maternal and fetal blood flow velocities.

SummaryIn a routine prenatal screening programme (16–18 weeks of pregnancy), consisting of 28670 ultrasound screening procedures, three cases with transient cystic hygroma and three with transient chylothorax were identified. The perinatal and the long term outcome of these fetuses is presented.