Autoantibodies to prothrombin and phosphatidylserine/prothrombin-complexes: do they contribute to the serodiagnosis of primary and secondary anti-phospholipid syndrome?

The diagnostic and clinical relevance of Ab to pure and phosphatidylserine-complexed prothrombin for primary and secondary APS was investigated in a total of 357 patients with (n = 169) and without (n = 188) connective tissue diseases. The overall frequency of anti-prothrombin Ab in sAPS, pAPS and patients without APS-related symptoms were found to be 50.0, 37.5 and 22.0%, respectively. From a total of 72 anti-prothrombin-positive samples, 12.5% were specific for pure prothrombin, 31.9% for phosphatidylserine/prothrombin-complexes and 55.6% recognized both antigenic forms. The simultaneous occurrence of other anti-phospholipid Ab was observed in 84% of all sera. Both types of anti-prothrombin Ab are significantly associated with lupus anticoagulant activity, but only Ab to pure prothrombin display such a relationship to clinical manifestations of APS. Based on these results, it cannot be recommended at present to include anti-prothrombin assays in the routine procedure for the serodiagnosis of APS. However, patients negative for lupus anticoagulant and typical APS-related anti-phospholipid Ab should be tested for anti-prothrombin reactivity, favoring, mainly due to its higher specificity, the ELISA containing pure prothrombin as antigen.

Reactivity profiles of autoantibodies to different phospholipids and the phospholipid-binding protein beta2-glycoprotein I in patients with clinical symptoms related to thromboembolic and/or vasculopathic events with or without connective tissue diseases.

To study the antigenic and epitope specificities of anti-phospholipid Ab in detail, we investigated 177 patients without (62 with APS-related systemic clinical symptoms, 115 with microangiopathies) and 164 patients with connective tissue diseases (CTD). Ab associated with primary APS (pAPS) seem to show a restricted specificity (phospholipid/beta2-GPI-complexes), whereas those in secondary APS (sAPS) react additionaly with pure beta2-GPI. Simultaneously, beta2-GPI-independent Ab were also frequently present in both conditions (50% of all Ab-positive sera). In CTD patients, the reactivity profile "pure beta2-GPI + phospholipid/beta2-GPI-complexes" is significantly associated with clinically manifest sAPS. Comparing cardiolipin and phosphatidylserine as antigenic target, the overall concordance (crossreactivity?) between both assays was lower than expected (52%), being highest in pAPS (87%) and sAPS (65%). Based on these results, a two-step procedure for reliable serological diagnosis of APS could be recommended: Ab-screening using a mix of phospholipids complexed with beta2-GPI (sensitivity > 90% for Ab concentrations above 20 U/ml) followed by an assay allowing the simultaneous detection of all relevant antigenic and epitope specificities.

Is the Zona pellucida thickness of metaphase-II oocytes in an IVF/ICSI program influenced by the patient's age?

Zona pellucida (Z.p.) thickness is believed to be considerably influenced by hormonal stimulation. Assessments of the influence of the patient's age on Z.p. thickness have been at variance. In our study we wanted to investigate, among several other parameters, the age of the patient as a possible factor influencing Z.p. thickness. Prior to intracytoplasmatic sperm injection (ICSI) we determined the mean thickness of the Z.p. of 843 metaphase-II oocytes from 100 patients, which had been obtained after ovarian stimulation in an in vitro fertilization (IVF)/ICSI program. The mean thickness of the Z.p. was significantly positively correlated with the age of the patient (p = 0.000, r = 0.129). When the intraindividual mean values of Z.p. thickness (n = 100) were used, a positive correlation with age (p = 0.174, r = 0.137) remained. However, this correlation was no longer significant. It is concluded that, beside other factors, a thicker Z.p. could be responsible for the possibly lower fertilization rate of older patients in a conventional IVF program.

Chimerism in a fertile woman with 46,XY karyotype and female phenotype.

We report on the unexpected finding of a 46,XY karyotype in a 30 year-old woman with normal ovarian function and a former pregnancy at 17 years of age. Chromosome analysis was performed prior to intracyoplasmic sperm injection (ICSI), due to infertility of her husband. Repeated chromosome analysis in lymphocytes of the female resulted in a normal male karyotype. Fluorescence in-situ hybridization (FISH) analysis of cultured lymphocyte interphase nuclei detected in 99% of the cells one X and one Y chromosome-specific signal respectively, whereas two X chromosome-specific signals were observed in only 1% of the nuclei. Chromosome analysis of fibroblasts of ovarian and muscular tissues as well as of skin revealed a normal female karyotype (46,XX). Chimerism could be proven by variable number of tandem repeats (VNTR) analysis. Since the case history of the patient revealed that her twin brother died shortly after birth, it can be assumed that chimerism is caused by feto-fetal transfusion during pregnancy and delivery of the proposita.

[Is there an increase of serum antisperm antibodies following surgery in the cervical transformation zone for cervical intraepithelial neoplasia (CIN)?]. / Führen aufgrund einer zervikalen intraepithelialen Neoplasie (CIN) durchgeführte Operationen an der zervikalen Transformationszone zu einem Anstieg humoraler Antispermatozoen-Antikörper?

OBJECTIVE: This prospective controlled study was performed to investigate whether operative procedures of the uterine cervix lead to a change in the titre of humoral antispermatozoal antibodies. MATERIAL AND METHODS: Humoral antispermatozoal antibodies were measured using an ELISA in 15 patients undergoing cervical scraping, 20 having conisation, 10 having a loop excision before and at least 3 months after surgery as well as in 10 fertile women as a control group. RESULTS: There were no significant differences in age between groups, in the distribution of initial and final levels of humoral antispermatozoal antibodies (IgG, IgA), and no significant change of the antibody titres (pre- and postoperative) within the individual groups. CONCLUSIONS: In patients of fertile age, the formation of humoral isoantibodies does not have to be taken into account in selecting the method of diagnosing and treating cervical intraepithelial neoplasia (CIN).

A comparative study of the hemostatic effects of two monophasic oral contraceptives containing 30 mu(g) ethinylestradiol and either 2 mg chlormadinone acetate or 150 mu(g) desogestrel.

OBJECTIVES: To determine the effect of two low-dose monophasic oral contraceptives containing either 2 mg chlormadinone acetate or 150 microg desogestrel on blood clotting and fibrinolysis. METHODS: In vivo markers of intravascular coagulatory and fibrinolytic activity were measured in 45 volunteers randomly assigned to a 6-month treatment with one of the two study preparations. RESULTS: During oral contraceptive use, the procoagulatory activity increased (increased prothrombin fragment 1+2), the anticoagulatory capacity changed (increased protein C activity, decreased activated protein C sensitivity, decreased protein S activity and decreased antithrombin III activity) and the fibrinolytic system was activated (increased concentrations of plasmin-antiplasmin complexes and D-dimer as well as total fibrin degradation products). There were no relevant differences between the two medication groups. CONCLUSION: Our results demonstrate that both oral contraceptive preparations have comparable effects on the hemostatic system. There was a shift towards a new equilibrium of hemostatic activities, both coagulatory and fibrinolytic, at a higher turnover rate. Changes did not exceed the range of normal variation and were comparable to the published effects of other low-dose oral contraceptives. There was no evidence ofa differential risk of deep vein thrombosis between the two preparations.

[Pregnancy and hormone replacement therapy in a patient with resistant ovary syndrome]. / Schwangerschaft unter Hormonersatztherapie bei einer Patientin mit einem passageren "Resistant-Ovary-Syndrome".

We report on the case of a 32-year-old woman with "resistant ovary syndrome". The patient received hormone replacement therapy sequentially with 2 mg estradiol valerate and 2 mg estradiol valerate/0.15 mg levonorgestrel (Klimonorm, Jenapharm, Germany) respectively, because of secondary amenorrhea and premature menopause. Under this therapy she conceived and had a delivery at term following an inconspicuous pregnancy. The case report emphasizes the rare but possible spontaneous remission of "resistant ovary syndrome" as a variant of premature menopause and is discussed in terms of the literature.

[Persistent anovulation following laparoscopic electrocoagulation of the ovarian surface in a patient with polycystic ovary syndrome (PCOS)]. / Persistierende Anovulation nach laparoskopischer Elektrokoagulation der Ovaroberflächen bei einer Patientin mit einem Polyzystischen-Ovar-Syndrom (PCOS).

We report on a 32-year-old woman with polycystic ovarian syndrome (PCOS) who showed no ovarian reaction (oestradiol increase, leading follicle) to clomiphene and gonadotropin stimulation before and after laparoscopic electrocoagulation of the ovarian surface (LEOS) although hormone values (LH-FSH ratio, androstenedione) after LEOS were within normal range. The case is discussed in terms of the literature.

[Cavernous hemangioma of the umbilical cord]. / Kavernöses Hämangiom der Nabelschnur.

We report the case of a cavernous hemangioma with a recently developed hematoma of the umbilical cord. Because of a threatening intrauterine asphyxia an operative vaginal delivery was performed followed by pulmonary disturbance of adaptation and anemia with transfusion. Possible complications are discussed both in terms of the case-history and literature.

Fertility and pregnancy outcome after myomectomy in sterility patients.

OBJECTIVES: To examine total pregnancy rate, pregnancy rate in relation to pretreatment with GnRH-analogues, the frequency of myoma recurrencies and the influence of size, number and localization of removed myomata on pregnancy rate and outcome in infertility patients after myomectomy. STUDY DESIGN: A comparative, retrospective non-randomized clinical study involving 67 patients with desire for children and no other recognizable infertility factor. Myomectomy had been performed between 1985 and 1993. Most patients had been operated by laparotomy using microsurgical instruments and techniques. Thirty-three patients had been treated with a GnRH agonist for usually 3 months, and in 34 patients the operation was performed without pretreatment. Patients were followed up to June, 1994. All patients were mailed a questionnaire and invited to an ultrasound examination. RESULTS: Thirty-nine of the 67 patients (58.2%) became pregnant, and a total of 51 pregnancies were observed. Of the women who actually conceived, 61.5% did so within the first year. There was no significant difference in pregnancy rates between patients who had been pretreated with GnRH agonists and those who had not. However, 1 year after the operation the group of GnRH-treated women was significantly overrepresented among those already pregnant (P = 0.02). Sonografical examination revealed in 31 out of the 67 patients (46.3%) recurrent myomata > 1 cm in diameter. There was no statistically significant difference in the pregnancy rates between patients with and without recurrencies. However, there was a significant tendency toward a loss or short duration of the pregnancy due to spontaneous abortion and premature delivery in patients with recurrent or persistent myomata (P < 0.01). Pregnancy rate was significantly lower in patients with more than five myomata removed (P < 0.001). In the group with a larger myoma volume the pregnancy rate was significantly higher than in the group with the smaller one (P < 0.01), possibly indicating that the size on removal of myomata is an important factor for infertility patients. Concerning the localization of the removed myomata, no statistically significant difference was found in the pregnancy rates between various localizations. Of the 51 pregnancies, 31 (60.8%) led to a delivery, vaginal in 13 cases (41.9%) and 18 times by Caesarean section (58.1%). Of the pregnancies that were lost, 39.2% were due to spontaneous abortion or ectopic pregnancy. CONCLUSIONS: Our study supports reports on the benefits of myomectomy, performed with the appropriate technique, in patients with otherwise unknown cause of infertility. It shows, additionally, that characteristics of myomata, such as number and size, may influence postmyomectomy pregnancy rates.

Human follicular fluid levels of endothelins in relation to oocyte maturity status.

The levels of endothelins 1 and 2 (ET-1 and ET-2) have been examined in 415 follicular fluids of 57 women participating in the IVF-ET programme in the University Women's Hospital, Marburg, in relation to the morphological appearance ("maturity") and fertilizability of harvested oocytes as well as to the levels of inhibin, FSH, IGF-1, estradiol and progesterone. Follicular aspiration was done transvaginally in all patients after down regulation with nafareline and ovarian stimulation using urofollitropin and menotropin. Ovulation was induced by hCG. ETs were measured by RIA using commercial kits supplied by Peninsula Laboratories, Belmont, CA. For FF samples, ET-1 and ET-2 RIAs were revalidated. Immunoreactive ET-1 was detectable in all follicular samples, the average level being 18.5 +/- 11.8 pg/ml, ET-2 was present only in 67.5% of the samples, the average level being 13.6 +/- 16.3 pg/ml. There was no significant difference in the average levels of ET-1 in the fluids of small, medium and large follicles. However, there was a significantly higher level of ET-2 in the fluids of medium compared to large follicles and there was a negative correlation of the ET-2 levels to the volume of the follicle (p < 0.01) which suggests that ET-2 could play a role during the maturation of the ovarian follicles. Unlike ET-1, the mean concentrations of ET-2 were significantly higher in the fluids with oocytes which could be fertilized and cleaved than in those with oocytes which did not fertilize or cleave, thus indicating a role for ET-2 in the process of oocyte maturation. No correlations of ET levels were found with the levels of inhibin, FSH, estradiol and progesterone. However, ET-2 levels significantly correlated with the levels of IGF-1 (p < 0.001) indicating a possible synergistic effect of endothelins and IGF-system. In conclusion, this study is further evidence for a physiological role of the ETs in the human ovary.

[Histology and cytology of laparoscopically operated "simple ovarian cysts"]. / Histologie und Zytologie laparoskopisch operierter "simpler Ovarialzysten".

In a retrospective study the histopathological findings of 127 laparoscopically operated unilocular anechoic smooth-walled ovarian cysts have been correlated with clinical characteristics (age, duration of observation, complaints, hormonal treatment), size by ultrasound, kind and colour of cysts content as well as cytological findings. The age of patients differed from 16-61 years (mean +/- s: 36 +/- 16). The histopathologic findings yielded 15 (11.8%) functional cysts, 30 (23.6%) persistent corpus luteum cysts, 9 (7.1%) endometriomas, 7 (5.5%) cystic teratomas, 9 (7.1%) undifferenciated cysts and 57 (44.9%) cystadenomas. There were no differences between histopathologic diagnosis groups according to age and cysts size by ultrasound. Functional cysts with complaints (n = 6) may explain that the observation time in 60% of all functional cysts was smaller than 6 weeks, whereas persistent corpus luteum cysts, endometriomas, cystic teratoma and cystadenomas had been observed for longer than 6 weeks in more than two thirds. Intraoperative evaluation of cysts content as "chocolate"-like was suspicious of endometriomas, but was also present in cysts of other histopathological findings. By means of cytology, endometrioma (siderophages) was suspected in 44.4% and a cystadenoma in 42.1% of all histopathologically verified cases. In all, the cytologic findings were useful for correct histopathological diagnosis in only 33.9% of all 127 cases. It is concluded that differential diagnosis of simple ovarian cysts is not possible by clinical characteristics, neither by ultrasound nor by cytological evaluation. Ovarian cysts should be observed for at least two hormonal cycles. A hormonal treatment by combination preparations containing high doses of oestrogen is also recommended. In cases of persisting ovarian cysts laparoscopic removal is necessary.

[Extrauterine pregnancy after hormonal postcoital contraception]. / Extrauteringraviditäten nach hormoneller Postkoitalkontrazeption.

Postcoital contraception with estrogen-gestagen-combinations is a highly effective emergency measure in cases of unprotected sexual intercourse at midcycle. Pregnancies after hormonal postcoital contraception are rare and ectopic pregnancies are said to be an extreme rarity. At the Department of Obstetrics and Gynecology of the Philipps-University Marburg we could observe two women with ectopic pregnancies after administration of a ethinyestradiol-levonorgestrel combination (Tetragynon, Schering, Berlin). Both patients were operated by pelviscopy. We could not found a clear causal relationship between the administration of hormonal postcoital contraception and ectopic pregnancies, because both women had intrauterine operations in her history and therefore a certain level of tubal damage could not ruled out. Nevertheless, in cases of hormonal postcoital contraception a follow-up check after 3 weeks should be done and it should be kept in mind that ectopic pregnancies may occur, especially in patients with risk factors.

[Possibilities of endoscopic diagnosis and therapy in reproduction medicine]. / Möglichkeiten endoskopischer Diagnostik und Therapie in der Reproduktionsmedizin.

Endoscopic minimal invasive procedures have opened new horizons for preventive care and treatment in reproductive medicine. They provide best conditions for careful handling of tissues and preservation of organs. After exclusion of functional sterility factors, the basis of any further treatment is obtained by diagnostic pelviscopy, hysteroscopy and salpingoscopy, respectively falloposcopy, this even more for the endoscopic therapy of tubarian and uterine sterility factors as well as endometriosis. A large domain in the use of endoscopy is the organ and fertility preserving surgery in younger women. This applies mainly for the pelviscopic treatment of ectopic pregnancies and pelviscopic/hysteroscopic myomectomy. Despite of all controversial discussions pelviscopic ovarian surgery has many advantages for women who desire further pregnancies. Falloposcopy enlarges the possibilities for the diagnosis and treatment of ectopic pregnancies. More randomized studies are necessary in order to estimate the indications and advantages of endoscopic procedures. A wide and efficient use of these promising techniques requires an early and appropriate training of all gynecologic surgeons.

[The effect of low-dose pre-ovulatory progesterone administration on the outcome of in-vitro fertilization (IVF) and intra-tubal gamete transfer (GIFT)]. / Zum Einfluss niedrigdosierter präovulatorischer Progesterongaben auf die Ergebnisse von In-vitro-Fertilisation (IVF) und intratubarem Gametentransfer (GIFT).

The influence of application of low-dose progesterone 4 hours before induction of ovulation by HCG on the outcome of IVF and GIFT was investigated in a bilateral study. The number of patients was 38 from both clinics for IVF and 36 for GIFT. With a pregnancy rate of 35.3% and 17.6% of ongoing pregnancies per transfer the results of the study are much better than before. The rather low number of patients and the low rate of transfers relativate these results. After GIFT an elevated abortion rate leads to only 11.1% ongoing pregnancies following a pregnancy rate of 33.3%. The effect of progesterone supplementation on the LH-peak and the endometrium should be further investigated to find new ways to increase success of IVF and GIFT treatment.

[Spermatocyte antibodies in serum and follicular fluid of IVF and GIFT patients]. / Spermatozyten-Antikörper im Serum und in der Follikelflüssigkeit von IVF- und GIFT-Patienten.

With a new SPAK-ELISA test system (Seratec GmbH) we determined sperm antibodies in sera of 60 IVF, 11 GIFT patients and their husbands. We evaluated sperm antibodies in sera of 12 IVF (20.0%), 3 GIFT (27%) and 3 males with normozoospermia parameters (4.2%). Compared to seronegative patients either the number of oocytes and their quality as the fertilization- and embryo transfer rate during the IVF/GIFT procedure were not affected. No intact pregnancy occurred in cases of sperm antibodies in sera. In 16.6% of all seropositive IVF patients the detection of sperm antibodies in the follicular fluids correspond to sera. We recommend to remove autologous serum for the oocyte culture in cases of sperm antibodies in serum of IVF patients.

[Problems in treatment of sterility in developing countries--experiences with sterility consultation in Gondar/Ethiopia]. / Probleme der Sterilitätsbehandlung in Entwicklungsländern--Erfahrungen mit einer Sterilitätssprechstunde in Gondar/Athiopien.

101 women were treated because of sterility in the Gondar College of Medical Sciences, Gondar/Ethiopia, in the years 1987/88. The results revealed some typical difficulties in diagnosis and treatment of sterility in developing countries, arising from limited technological facilities and special characteristics of the group of treated patients. In 61 women a final diagnosis could be made. The main cause of sterility was complete tubal occlusion in 65.6% of the cases due to a high incidence of pelvic inflammatory diseases in the investigated patients. Ovarian causes accounted for only 18%. The importance of the male factor was not evaluable due to a traditionally conservative attitude of most men against sterility investigations. Chromolaparoscopy in combination with endometrial biopsy in the second half of the cycle were well suitable for clearing most of female causes of sterility.

[Hormone profile and follicle development in ovarian stimulation treatment for in vitro fertilization. II. Prolactin, estradiol and progesterone profile]. / Hormonprofile und Follikelentwicklung unter ovarieller Stimulationsbehandlung für die In-vitro-Fertilisation. II. Mitteilung: Prolaktin-, Estradiol- und Progesteronprofile.

144 patients were treated by 5 different stimulation protocols in the IVF-program of the University Women's Hospital Rostock (Clomiphene/hCG, Clomiphene/Anthrogon/hCG, Pergonal/hCG, Anthrogon/hCG, Folistiman/hCG). Estradiol-17 beta and progesterone were determined during the follicular phase of 172 cycles by RIA. The results were compared between the treatment groups by means of Student's t-test or Mann-Whitney's nonparametric test. Additionally, in 37 cycles prolactin was determined. The levels of estradiol-17 beta in all treated groups were higher as compared with spontaneous cycles. Between the groups statistically significant differences were found in start and velocity of E2-rise, in the average level of E2, and in the level of preovulatory peaks. The latent phase of stimulation was significantly longer in patients treated with pergonal than in Anthrogon treated patients. Moreover, in the Anthrogon group the rate of "high responder" was higher. On average, in patients with a very fast growth rate of estradiol-17 beta (greater than 1.9 nmol/l) during the late follicular phase the percentage of less mature oocytes was increased after follicular puncture. The levels of progesterone started to rise in all groups between day-2 and -1 (day 0: day of LH-peak). On day 0, patients with Pergonal and Anthrogon had the significantly highest level. Levels above the 1s-range occurred in 12 patients during the follicular phase. This elevation of progesterone took place in 3 patients without any rise of basal LH-levels. 80.4% of 37 patients investigated were found to have prolactin levels above 500 mE/l during the late follicular phase. This transient hyperprolactinemia correlated with the rise of estradiol levels and continued during the early and mid luteal phase. Hence preventive administration of bromocryptine appears to be advisable in cycles stimulated with gonadotropins.