[Heterotopic pregnancy after in vitro fertilization]. / Heterotop graviditet efter in vitro fertilisering.

Until December 1991, 1171 pregnancies had been established in Denmark after in vitro fertilization and embryo transfer (IVF-ET). Thirteen of these pregnancies were heterotopic (1.1%). Three patients were asymptomatic, four patients presented with an acute abdomen, five had abdominal pain and only two patients had vaginal bleeding. In five cases the diagnosis of heterotopic pregnancy was made by ultrasound, while eight cases were diagnosed at the time of surgery. Eleven patients were treated in the first trimester, while two patients were treated at 23 and 38 weeks of gestation, respectively. In nine of the thirteen cases the intrauterine pregnancy resulted in term delivery. Heterotopic pregnancy occurred in 1% of pregnancies following IVF-ET. Abdominal pain was the predominant symptom, while vaginal bleeding was absent in the majority of women. In most cases removal of the ectopic gestation allowed the intrauterine pregnancy to proceed until term.

[Fertilization in vitro. A review over the medical indications and suggestion to unified guidelines for public fertility clinics in Denmark]. / In vitro fertilisering. En oversigt over medicinske indikationer og forslag til foelles retningslinier ved de offentlige danske fertilitetsklinikker.

Medical indications for in vitro fertilization and embryo transfer (IVF-ET) internationally and in Denmark are reviewed. Reports from large international centres document that tubal infertility, unexplained infertility, endometriosis and male infertility are equally good indications for IVF. Traditionally, tubal infertility has been the only medical indication qualifying for IVF treatment within the National Health Service in Denmark. Thus, in this country, couples with unexplained and male infertility and with endometriosis have to pay up to 25,000 D.Kr. per IVF-ET treatment in private fertility clinics. Since there is no scientific basis for this discrimination, it is urged that the present rules are changed, so that couples with unexplained and male infertility and endometriosis are also allowed IVF treatment free of charge in the public fertility clinics.

[Ovum donation. A review of and a suggestion to unified guidelines for treatment at public fertility clinics in Denmark]. / Aegdonation. En oversigt samt forslag til foelles retningslinier for behandling ved de offentlige danske fertilitetsklinikker.

The most common indication for oocyte donation is ovarian insufficiency due to premature menopause or resistant ovarian syndrome and ovarian dysgenesis with either normal or abnormal (e.g. Turner's syndrome) karyotype. In Denmark, oocyte donation must be anonymous, and the donors have to be other infertile patients undergoing in vitro fertilisation (IVF), treatment. It is suggested, that the National Health Service offers oocyte donation to hypergonadotropic women with ovarian insufficiency, as well as to a few other groups who fulfil the criteria for IVF treatment, but where this treatment cannot be completed. Oocyte donors must be less than 35 years old, physically and mentally healthy and without major genetic diseases in the family. The donor must be screened for HIV, hepatitis, syphilis, chlamydia and gonorrhoea. We propose that those patients who have more than six oocytes aspirated, allowing "surplus" oocytes to be donated. It is also proposed that the departmental order from the Ministry of Health be changed, so that normally fertile women are allowed to donate oocytes. Oocyte donation should be reported to a central authority.

[Freezing of human embryos. A review of and a suggestion to unified guidelines for treatment at public fertility clinics in Denmark]. / Nedfrysning af menneskelige aeg. En oversigt samt forslag til faelles retningslinier for behandling ved de offentlige danske fertilitetsklinikker.

In Denmark, legislation has made cryopreservation of human oocytes and embryos possible since October 1992. The legislation is reviewed. Cryopreservation of embryos constitutes a significant improvement of infertility treatment. The number of oocyte pick-ups and the number of embryos transferred can be reduced without compromising the total likelihood of success of in-vitro fertilization (IVF) treatment. According to Danish law, frozen embryos can only be stored for one year. This limit will interfere with patient expectations in numerous cases, and the time limit should be expanded. Moreover, freezing of embryos should be allowed in connection with oocyte donation programmes.

Heterotopic pregnancies after in-vitro fertilization and embryo transfer--a Danish survey.

Thirteen cases of heterotopic pregnancy were diagnosed among 1171 pregnancies established in Denmark after in-vitro fertilization and embryo transfer (IVF-ET). Thus the frequency of heterotopic pregnancy was 13/1171 or 1.1%. In five cases the diagnosis of heterotopic pregnancy was made by ultrasound at 6-9 weeks of gestation; three of these patients were asymptomatic, while two patients presented with abdominal pain and vaginal bleeding. All these patients had an unruptured ectopic pregnancy. Eight cases were diagnosed at the time of surgery; all these patients presented with abdominal pain. Only two of the 13 patients had vaginal bleeding. In nine of the 13 cases the intra-uterine pregnancy resulted in term delivery, while one pregnancy is ongoing. In pregnancies following IVF-ET, this diagnosis should particularly be considered in cases with abdominal pain; vaginal bleeding may be absent. Ultrasound examination may lead to early diagnosis even in asymptomatic cases. In most cases, removal of the ectopic gestation will allow the intrauterine pregnancy to proceed to term.

Acute tissue effects during transcervical endometrial resection.

The acute tissue effects of transcervical endometrial resection (TCRE) with a standard Iglesias resectoscope using glycine 1.5% for irrigation were studied in 8 women prior to hysterectomy. Combinations of 80 or 120 W cutting current with blend 1 or 2 were applied for endometrial resection, preceded by cornual endometrial coagulation with the roller ball electrode with a coagulation effect of 40 or 60 W. The temperature was measured at the uterine vessels, ovarian ligaments and serosal surface. The increase in temperature at the serosal surface was 2.0 degrees C during cornual coagulation and 0.3 degrees C during endometrial resection, independent of the current effect applied. The maximum depth of tissue damage was 1.7 mm. No change in temperature was found at the uterine vessels or ovarian ligaments. The tissue destruction and the increase in temperature of the uterine surface are minimal, and TCRE offers excellent histological material. Careful coagulation/resection in the cornual and isthmus regions is recommended.

Effects of vasodilators on isolated human uteroplacental arteries.

The effects of the vasodilator drugs hydralazine, labetalol, prazosin, and nitrendipine were studied on responses to K+ (124 mmol/L), noradrenaline, vasopressin, and angiotensin II in small human maternal intramyometrial arteries and on responses to K+, prostaglandin (PG) F2 alpha, and angiotensin II in fetal stem villous arteries. The vessels were dissected from biopsy specimens obtained during term cesareans and mounted in organ baths. Hydralazine failed to inhibit responses to any of the agonists tested in the fetal and maternal arteries. Labetalol and prazosin decreased responses to noradrenaline but did not affect contractions induced by the other agonists in maternal arteries. In fetal arteries, which did not respond to noradrenaline, no effects of labetalol and prazosin were found. Nitrendipine inhibited responses to all the agonists tested in maternal arteries. In fetal preparations, the drug decreased responses to K+ and PGF2 alpha but did not affect contractions induced by angiotensin II. Vasodilator drugs applied for treatment of pregnancy-induced hypertension show differential effects on human maternal and fetal uteroplacental arteries, depending on their mode of action and the agonists responsible for the contractile activation in these vessels.

[Transabdominal chorion villus biopsy following abnormal ultrasonic findings in the second trimester]. / Transabdominal chorion villus biopsi ved abnormt ultralydfund i 2. trimester.

If oligohydramnios, growth retardation or foetal malformations are demonstrated by ultrasonic scanning in the second or third trimesters, this implies that the risk of chromosome anomalies is significantly increased. In cases such as these, determination of the foetal karyotype may therefore be indicated. Until recently, amniocentesis has been employed for this but the results of the chromosome investigation are not available until two to three weeks after the intervention. The delay between amniocentesis and the result of chromosome investigation imposes a mental strain on the pregnant woman. Three patients with abnormal ultrasonic findings in the second trimester were, therefore, submitted to transabdominal chorion villus biopsy and, in all three cases, a karyotype was available within 48 hours. Chorion villus biopsy in the second (and third) trimester is indicated in pregnancies in which oligohydramnios, growth retardation or foetal malformations have been demonstrated by ultrasonic scanning, in cases where referral for antenatal diagnosis is very late and when chromosome investigation after amniocentesis proves unsuccessful and repeated amniocentesis would result in an unacceptably late result.

Effect of endogenous vasoconstrictors on maternal intramyometrial and fetal stem villous arteries in pre-eclampsia.

The contractile responses to various endogenous vasoactive agents were investigated in isolated human uteroplacental arteries from normotensive (NT) patients and patients with pre-eclampsia (PE) undergoing caesarian section. Tissue samples were obtained from the uterine incision and from macroscopically normal cotyledons. Vascular ring preparations of intramyometrial and stem villous arteries (length 1.0-1.3 mm, outer diameter 400-600 microns) were dissected and mounted in organ baths and isometric tension was recorded. Concentration-response relationships for vasopressin (VP), oxytocin (OX), angiotensin II (Ang II), noradrenaline (NA), 5-hydroxytryptamine (5-HT), prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) were assessed. For each compound, the mean maximum contractile effect (Emax) and the drug concentration producing half-maximal response (EC50) were determined. In intramyometrial arteries from NT and PE patients, VP, Ang II, NA, 5-HT and PGF2 alpha induced contraction while OX and PGE2 produced weak or no responses. Preparations from PE patients showed higher Emax values, while no differences in EC50 were found between the two groups. In fetal stem villous arteries, Ang II, 5-HT, PGF2 alpha and PGE2 induced contractions, while VP, NA and OX produced weak responses. No differences in Emax or EC50 values were found between the fetal vessels of PE and NT patients. No qualitative differences were demonstrated in response to the agents tested between the vessels (fetal and maternal) from NT women at term and PE patients. However, the results may reflect quantitative differences, suggesting increased contractility of maternal uteroplacental arteries from women with PE.

[In vitro fertilization and embryo transfer at the community hospital in Arhus]. / In vitro fertilisation og embryotransferering ved Arhus Kommunehospital.

Treatment of tubal infertility with in vitro fertilization and embryo transfer (IVF-ET) was introduced in the gynaecological/obstetric department of Arhus Municipal Hospital in February 1988. The principles of treatment are described. During the first ten months, 305 therapeutic cycles were carried out and clinical pregnancy occurred in 20.2% of the cycli after transfer of pre-embryos.

Effects of vasoactive intestinal polypeptide and substance P on human intramyometrial arteries and stem villous arteries in term pregnancy.

The effects of vasoactive intestinal polypeptide (VIP) and substance P on isolated human intramyometrial arteries and fetal stem villous arteries obtained from term pregnant women were compared. Ring preparations of small intramyometrial arteries and fetal stem villous arteries obtained at caesarean section were mounted in organ baths, and isometric tension was recorded. None of the peptides affected resting tension. In intramyometrial arteries precontracted by vasopressin (2.8 x 10(-9) M) both substance P (10(-12) to 10(-8) M) and VIP (10(-8) to 10(-6) M) caused relaxation. In fetal stem villous arteries precontracted by prostaglandin F2 alpha (10(-5) M) cumulative addition of substance P (10(-11) to 10(-6) M) did not produce significant changes in tension as compared with controls, while addition of single doses produced moderate relaxation. VIP (10(-8) to 10(-6) M) induced relaxation with similar effects for the addition of cumulative and single doses. The responses to VIP and substance P remained unaffected after pretreatment by atropine (10(-6) M), propranolol (10(-6) M), and indomethacin (10(-6) M). The results support a role for VIP and substance P in the regulation of uteroplacental blood flow in term pregnancy.

Effects of some neurotransmitters and prostanoids on isolated human intracervical arteries.

Human cervical tissue specimens were excised after hysterectomy at various phases of the menstrual cycle (n = 12), and small intracervical arteries were dissected free by microtechnique. Ring preparations of the vessels were prepared and mounted in organ baths, and isometric circular tension was recorded. Norepinephrine, 3 X 10(-8) to 10(-5) mol/L, produced concentration-dependent contractions, whereas 3 X 10(-7) to 10(-6) mol/L prostaglandin F2 alpha inconsistently produced weak contractions and slightly increased tension induced by 10(-5) mol/L norepinephrine. Prostaglandin I2, 10(-9) to 10(-6) mol/L, prostaglandin E2, 3 X 10(-9) to 10(-6) mol/L, vasoactive intestinal polypeptide, 10(-9) to 10(-7) mol/L, and substance P, 10(-12) to 10(-9) mol/L, induced relaxation of vessels precontracted by 10(-5) mol/L norepinephrine. It is suggested that several mechanisms for the local release of vasoactive compounds may influence cervical blood flow. Thus, sympathetic control of cervical blood flow may be modulated by peptide neurotransmitters such as vasoactive intestinal polypeptide and substance P and by local synthesis of prostaglandins E2 and I2.

Effects of VIP and PHM in human intracervical arteries.

The relaxing effects of vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) on human intracervical arteries were studied. Cervical tissue specimens were excised after hysterectomy at various phases of the menstrual cycle (n = 12) and small intracervical arteries were dissected free by microtechnique. Ring preparations of the vessels were prepared and mounted in organ baths, and isometric circular tension was recorded. None of the compounds showed any effects in unstimulated cervical arterial preparations. In vessels precontracted by noradrenalin 10(-5) M, VIP 10(-8) - 10(-6) M and PHM 10(-8) - 10(-6) M induced similar, concentration-dependent relaxation with a maximum effect of 73.2 +/- 12.7% relaxation for VIP 10(-6) M and 79.6 +/- 11.8% for PHM 10(-6) M, as compared to 10.7 +/- 3.1% decrease in tension for control preparations treated with solvent (mean +/- SE, n = 6). Simultaneous addition of VIP 5 x 10(-7) M and PHM 5 x 10(-7) M produced additive effects. Pretreatment with indometacin 10(-6) M, atropine 10(-6) M or propranolol 10(-6) M did not significantly influence these responses. Both peptides might be involved in regulation of blood flow in the human cervix.

Effects of human calcitonin gene-related peptide and substance P on human intracervical arteries.

The contractile effects of substance P and human calcitonin gene-related peptide (human CGRP) on isolated human intracervical arteries were studied. Human cervical tissue specimens were excised after hysterectomy at various phases of the menstrual cycle (n = 14) and small intracervical arteries were dissected free by microtechnique. Ring preparations of the vessels were prepared and mounted in organ baths, and isometric circular tension was recorded. Neither compound affected resting tension. Both peptides showed potent relaxing effects on vessels precontracted by noradrenaline 10(-5) M. Substance P exhibited the higher potency, while human CGRP showed the higher efficacy. The relaxing effects of the two compounds were unaffected by pretreatment with indomethacin 10(-6) M, propranolol 10(-6) M and atropine 10(-6) M. The results support a role for the two peptides in the regulation of cervical blood flow.

Effects of thiopentone or chlormethiazole on human placental stem villous arteries.

Small placental stem villous arteries were micro dissected from specimens obtained at normal term vaginal delivery (n = 25). Ring preparations of the vessels were mounted in organ baths and isometric tension was measured. Prostaglandin F2 alpha (PGF2 alpha) 10(-7)-10(-4) mol litre-1 produced concentration-dependent contractile responses that were inhibited by thiopentone 10(-4)-10(-3) mol litre-1 and by chlormethiazole 3 x 10(-4)-3 x 10(-3) mol litre-1. Thiopentone 10(-4)-10(-3) mol litre-1 and chlormethiazole 3 x 10(-4)-3 x 10(-3) mol litre-1 decreased the tension in vessels previously treated with PGF2 alpha 10(-5) mol litre-1. Chlormethiazole 3 x 10(-3) mol litre-1 inhibited, and thiopentone 10(-4)-10(-3) mol litre-1 abolished contractile responses to 5-hydroxytryptamine. Contractions induced by angiotensin II were inhibited by thiopentone 10(-3) mol litre-1 and chlormethiazole 3 x 10(-3) mol litre-1. The concentrations of the two drugs needed to affect contractile activation of isolated human stem villous arteries exceeded the free plasma concentrations reached during anaesthesia induced by the agents during Caesarean section, and the present results do not suggest any major effects of thiopentone or chlormethiazole on fetal placental vascular resistance during the clinical use of these drugs.

Relaxant effects of hexosamines on isolated small human placental arteries.

Wharton's jelly contains large amounts of hyaluronic acid, and glucosamine is an important constituent of this macromolecule. In order to evaluate the placental vascular effects of this aminosugar, small chorionic and stem villous arteries were dissected from placental specimens obtained at normal term vaginal deliveries (n = 15). Ring preparations were mounted in organ baths, and isometric wall tensions were measured. Glucosamine and its epimer galactosamine (5 X 10(-4) to 10(-2) M) produced marked relaxation of contractions induced by PGF2 alpha (10(-5) M) in both chorionic and stem villous arteries. The effect was unchanged after pretreatment with atropin, propranolol and indomethacin. The relaxant effect of the neutral sugar mannose was less pronounced compared with that of the hexosamines. Total tissue concentrations of placental hexosamines have been reported within the range needed to produce placental vascular relaxation in the present study. However, the major part of these compounds is integrated in macromolecules, and the tissue level of free hexosamine is probably far below the total concentrations. Accordingly, the effects of hexosamines demonstrated in the present study might not be of physiological importance in the regulation of fetal placental medial smooth muscle tension.

Acute effects of nitrendipine in pregnancy-induced hypertension.

The acute effects of a single, 20 mg oral dose of nitrendipine were studied in 10 women at between 32 and 42 weeks gestation with stable pregnancy-induced hypertension (PIH). Blood pressure (BP), maternal heart rate and fetal heart rate (FHR) were assessed for 8 h after nitrendipine intake together with the plasma levels of nitrendipine, noradrenaline, adrenaline, plasma renin activity (PRA) and vasopressin. The mean initial systolic/diastolic BP was 158 (SEM 3.7)/108 (SEM 2.7) mmHg. Within 1 h stable, reduced mean BP-levels of 141-145/90-95 mmHg were reached and maintained for 4 h after medication. This antihypertensive effect was closely related to the maternal plasma concentration of nitrendipine, which reached a maximum of 9.1 (SEM 2.6) ng/ml 3 h after tablet intake. After 4 h, systolic and diastolic BPs slowly increased in parallel to a successive decrease in plasma concentrations of nitrendipine. Maternal heart rate increased by less than 10%, while FHR remained unchanged. No hypotensive incidents occurred. The initial mean plasma concentrations of noradrenaline, adrenaline, vasopressin and PRA did not change during the treatment. No major maternal and no fetal side-effects were observed. Three of 10 patients experienced mild, transient facial flushing.