Elisabeth Johannisson

Effect of a combined oral contraceptive containing 3 mg of drospirenone and 30 μg of ethinyl estradiol on the human endometrium

OBJECTIVEnTo provide an in-depth assessment of the effects of the combined oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone (Yasmin, Schering AG, Berlin) on the endometrium by means of endometrial morphometry in comparison to an untreated cycle.nnnDESIGNnThe open, multicenter study consisted of one untreated precycle and 13 treatment cycles.nnnSETTINGnFour gynecologic clinics in Belgium, The Netherlands, and Switzerland were involved.nnnPATIENT(S)nForty women with a history of regular menstrual cycles.nnnINTERVENTION(S)nBefore the commencement of the trial, 3 months without any hormonal intake was obligatory. The first endometrial sample was done in the untreated precycle, adjusted to the day of LH peak plus 5 to 6 days. During the medication phase, endometrial samples were taken at cycle 3, 6 and 13.nnnMAIN OUTCOME MEASURE(S)nPrimary outcome measure of the study was the morphologic assessment of the endometrium with measures such as glandular diameter, glandular epithelial height, and number of vacuolated cells per 1,000 glandular cells. Furthermore, the endometrial thickness was measured by ultrasound.nnnRESULT(S)nAfter 13 cycles of medication use the endometrium had an atrophic appearance in 63% of the subjects. The size of the glands, the glandular epithelial height, and the number of glands per square millimeter were already significantly reduced after 3 months use. Histological and ultrasonographical evaluation of the endometrium indicated a suppression of the proliferative activity of the endometrium.nnnCONCLUSION(S)nThe combination of 30 microg of ethinyl estradiol with 3 mg of drospirenone induces changes of the endometrium that are comparable with other combined oral contraceptives and exhibits a marked antiproliferative effect on the endometrium. The medication was proven to be an effective oral contraceptive and revealed good cycle control characteristics.

Analysis of the karyotype and desoxyribonucleic acid content of uterine myomas in premenopausal, menopausal, and gonadotropin-releasing hormone agonist-treated females

OBJECTIVEnTo correlate the cytogenetics and the DNA content in uterine myomas.nnnDESIGNnProspective study in treated and untreated females.nnnSETTINGnTertiary University Center.nnnPATIENTSnPremenopausal, menopausal, and GnRH-agonist (GnRH-a)-treated patients.nnnINTERVENTIONnMyomectomy or hysterectomy.nnnMAIN OUTCOME MEASUREnKaryotype analysis and the DNA content measured by microfluorescence technique and expressed in fluorescence units.nnnRESULTSnThe mean DNA content in cells from karyotypically normal and karyotypically abnormal myomas, respectively, was 37.4 +/- 6.9 and 30.4 +/- 1.8 fluorescence units in premenopausal females, 30.3 +/- 5.3 and 28.7 +/- 0.9 fluorescence units in menopausal females, and 31.6 +/- 2.7 and 32.9 +/- 5.8 fluorescence units in GnRH-a-treated females.nnnCONCLUSIONSnForty percent of the myomas evaluated demonstrated an abnormal karyotype and had a significantly lower DNA content than the chromosomally normal myomas. After GnRH-agonist treatment, the DNA content was decreased in the euploid myoma group only.

Morphometric characteristics of endometrial biopsies after different types of ovarian stimulation for infertility treatment

OBJECTIVEnTo investigate whether various types of ovarian stimulation induce differences in endometrial development at the midluteal phase in infertile women.nnnDESIGNnAssessment of stromal and glandular compartments in endometrial biopsies using morphometric criteria.nnnSETTINGnInstitute for Hormone and Fertility Research, Hamburg, Germany.nnnPATIENTSnThe study included 18 women after treatment with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) (group I), 23 women after clomiphene citrate (CC)/hMG/hCG treatment (group II), and 12 women after CC stimulation (group III).nnnINTERVENTIONSnEndometrial biopsies and blood samples were taken simultaneously in the early to midluteal phase. To assess the time of ovulation, hormone analysis and regular checks by ultrasonography were performed.nnnMAIN OUTCOME MEASURESnMorphometric evaluation of glandular and stromal structures revealed an impaired endometrial development after various treatment protocols.nnnCONCLUSIONnOvarian stimulation in infertile women results in most cases in an elevation of steroid levels; however, the occurrence of an inadequate endometrial development might have an unfavorable influence on the outcome of implantation. Therefore, these findings may be of importance to the choice of treatment for infertility.

Morphometric analysis of the endometrium of infertile patients in relation to peripheral hormone levels

In an attempt to identify factors that may be responsible for reproductive failure, we compared endometrial biopsies taken from infertile patients during the luteal phase of spontaneous cycles (n = 18) with those taken after ovarian stimulation (n = 18). Morphometric analyses were performed and compared with peripheral estradiol (E2) and progesterone levels at the time of supposed implantation. In stimulated cycles the number of glands per square millimeter was positively correlated to the E2 level. The morphometric data point to a measurable difference between the study groups, indicating an insufficient secretory transformation of the tissue in infertile women when compared with a group of fertile women. The observations suggest that hormonal stimulation occasionally results in impaired development of the endometrial glands.

Oral contraceptives and hepatocellular carcinoma

undoubted, -and we should applaud the white knights progress, especially over the concept ofan essential drug list (24 May, p 1347). Nevertheless, the WHOs advice should not be above criticism, and its suggestions for primary care treatment in epilepsy are highly questionable, specifically its recommendation that phenobarbitone should be the first line anticonvulsant. Phenobarbitone is cheap and efficacious but has several drawbacks which render it peculiarly undesirable in poorly supervised settings in the developing world. Firstly, it is a drug of abuse, and in most countries is subject to special controls. I would not relish encouraging the prospect of a black market in government supplied barbiturate among addicts in the slums of the great Third World cities. Secondly, the safe use of phenobarbitone in epilepsy requires a consistent and reliable supply. The sudden withdrawal ofestablished phenobarbitone therapy in an epileptic is dangerous, with the frequent precipitation of withdrawal seizures and other withdrawal phenomena. The fact that abrupt discontinuation may result in status epilepticus was recognised 75 years ago, within a short time ofthe drugs introduction, and all experienced physicians will treat even its gradual withdrawal with considerable apprehension. Our advisers in Geneva many ofwhom incidentally are not practising clinicians-do not seem to have heeded this lesson. In my experience in developing countries in three continents the availability of phenobarbitone (and indeed other antiepileptic drugs) is notoriously unreliable. In rural hospitals drug supplies are often erratic and intermittent, and in the case of phenobarbitone this may have serious and sometimes fatal consequences. Ironically, the very cheapness of phenobarbitone in some countries exacerbates this problem of availability; because of its low profit margins the manufacturers seldom seem bothered to produce the drug in adequate quantities. These problems ofsupply are widespread in-Africa, Asia, and South America. Thirdly, there are the problems of the interaction of phenobarbitone with alcohol, a potentially serious public health issue. Fourthly, the risks-of death in overdose are greater than with other anticonvulsants. Finally, and very important, are the mental side effects of the -drug. In children drug induced hyperactivity is sometimesprofound, and at all ages depression, sedation, and intellectual slowing may occur. These toxic effects require careful monitoring, and many clinicians in the West no longer recommend this drug for first line treatment, and certaitly not in children. I sense double standards here. If a drug is not receommerkded in the West why should it be acceptable in developing countries? This is to place a hierarchy on mentalfunctioning in the developed and developing world, and it is cynical to pretend that this is anything but an expediency on the grounds ofcost. It is for individual governments to decide on the funding of health, but the WHO should not be party to such medical compronise.

A new method to study the process of implantation of a human blastocyst in vitro**Supported by grant 03X-3972 from the Swedish Medical Research Council, Stockholm, Sweden.

OBJECTIVESnTo develop a miniorgan culture of human endometrium dated according to the LH peak in order to study the process of implantation of a human blastocyst in vitro.nnnDESIGNnPreliminary results of a more extensive study with the same objectives.nnnSETTINGnHospital-based unit of reproductive health and university-related reproductive research laboratories.nnnPATIENTSnSix apparently healthy women with normal regular menstrual cycles providing endometrial material 4, 5 and 6 days after the LH peak.nnnINTERVENTIONnOne part of the biopsy was used for histologic dating. The other part was incubated in culture medium RPMI-1640 and exposed to the contact with one to three embryos fertilized in vitro.nnnMAIN OUTCOME MEASUREnBiopsy material before and after incubation was studied by morphometric methods in a light microscope. The histologic changes were recorded by photomicrographs.nnnRESULTSnImplantation of an embryo obtained 4 days after IVF penetrated the lining endometrial epithelium of a biopsy obtained 4 days after the LH peak and kept in vitro for 24 hours. The embryo was placed on the lining epithelium of the endometrium within 3 hours after the biopsy was taken.nnnCONCLUSIONnA new method to study the process of implantation of a human embryo in vitro has been described, allowing the embryo to penetrate the lining endometrial epithelium in a biopsy obtained at LH +4/+5.

Cyclic changes in human endometrial surface glycoproteins: a quantitative histochemical study**Supported by the Brown Craig Travelling Fellowship of the Royal Australian College of Obstetricians and Gynaecologists awarded to Robert Jansen, Swiss National Research Foundation grant 3.912-0.82, and by the World Health Organization Special Programme of Research in Human Reproduction, Geneva.

We used histochemical methods specific for carbohydrates on accurately timed endometrial biopsies to examine changes in quantity or electronegativity of the endometriums luminal glycocalyx through the menstrual cycle in normal fertile women. Electronegative glycocalyx was detectable light-microscopically throughout the menstrual cycle. On the third day after the luteinizing hormone peak, a significant increase (P = 0.005) in endometrial surface glycocalyx was evident along with the appearance, in endometrial glands, of material having the staining properties of acid mucus glycoprotein (MGP), which implies that after this materials production by the glands or by the surface epithelium, it becomes adsorbed onto the surface glycocalyx. This phenomenon was accompanied by an apparent decrease in glycocalyceal electronegativity as indicated by a shift from high iron diamine (pH 1.0) to alcian blue (pH 2.5) staining reactivity. Because the timing of the appearance of endometrial moderately acid MGP coincides with or precedes the time that the early fertilized embryo enters the endometrial cavity, a role for the MGP in embryo nutrition or in implantation is suggested.

Scanning Electron Microscopic Study of the Human Fallopian Tube. Report I. The Proliferative and Secretory Stages**Supported by Swedish Medical Research Council Grant B72-12-x-2712-04, Karolinska Institutet Stockholm, the Swedish International Development Authority, and The Ford Foundation and JEOL Inc.

An examination of the epithelial surface of the Fallopian tubes of 10 women treated by salpingohysterectomy or salpingectomy was performed with a scanning electron microscope. Different regions of the oviduct were studied during the midproliferative and late secretory phases to note differences in the ciliated and nonciliated cells as well as the distribution of the ciliae. It was found that the ciliae were unevenly distributed with more in the fimbral end and the ampulla and fewer in the intramural portion of the tube. Cyclic changes occurred in nonciliated cells during the secretory phase and the number and size of microvilli decreased and changed appearance. The ciliae changed somewhat in superficial structure became more granulated and lost vigor. These epithelial alterations as well as the distribution of the ciliae may have importance for the transport of the fertilized ovum.(AUTHORS MODIFIED)