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.

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.

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.

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.

[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.

[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.

[Results of an ultrasonic screening programme in the detection of intrauterine growth retardation]. / Ergebnisse eines Ultraschallscreeningprogrammes bei der Erkennung der intrauterinen fetalen Retardierung.

From January 1980 to July 1981 817 pregnant women were checked up by means of an ultrasonic screening programme. Ultrasonic measurement of the BPD and of the thoracic diameter were performed in the first trimester, between 21 and 30 and 31 and 40 weeks of gestation. For evaluation was used the diagram from Prenzlau and Issel. 72 out of the 817 women delivered a child with a birthweight below the 10th centile (GDR-Standards). From these children 65 (90,3%) were antenatally detected by ultrasonography. Hence, the sensitivity of the screening programme was 90,3%. The other parameters of the screening were: specifity 97,7%, positive predictive value 79,3%, negative predictive value 95,2%, effectivity 97,1%. The prediction of intrauterine growth retardation in the screening was significantly better compared to a group of 90 growth retarded children whose mothers were only examined by sonography sporadically. The average detection rate in both ultrasonic groups was 83,3%, but in contrast the percentage of clinically detected small-for-dates infants was only 15,4%.

[Developmental trends in reproduction medicine]. / Entwicklungstendenzen in der Reproduktionsmedizin.

In the last few years reproductive medicine has developed into a medical research field of its own. It deals with the theoretical and practical problems of human reproduction and is characterized by close cooperation between medical and scientific specialists both clinically and in research. Far-reaching social effects arise from the application of hitherto unknown research and treatment methods. The results of research in reproductive medicine led, due to the development of effective contraceptives, to a reduced connection between sexual intercourse and reproduction, and have made possible reproduction even without sexual intercourse, by means of artificial insemination and in-vitro fertilization. These latest and most exciting developments in reproductive medicine are based on and justified by the right of every couple to a child of their own. In-vitro fertilization and related treatments, eg. gamete intrafallopian transfer, are expected to dominate the treatment of the sterile couple in future. The social effects of the new techniques in reproductive medicine nessecitate the development of ethical standpoints, in which human welfare must predominate. In the GDR, in accordance with the recommendations of the "Ethics in medicine" working group, in-vitro fertilization using gametes of the same couple is ethically accepted, as is also oocyte and embryo donation, provided they aim to fulfil a couple's wish for a child. Surrogate mothers are rejected, however. The combination of in-vitro fertilization and genetic engineering could potentially be used in the treatment of certain types of hereditary disease, but there is also the possibility of misuse.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

[Current status of the development of interceptive agents]. / Zum Stand der Entwicklung von Interzeptiva.

An account is given of present applications of interceptively acting substances. Pharmaceuticals used so far for postcoital conception (oestrogens, gestagens, and combinations of these) are suitable for single application, but their regular use is limited by side-effects. Various approaches are being taken to the development of effective interceptives for high-continuity application but with low side-effects. Antigestagens, LHRH-analogues, and immunological contraceptives seem to be among the most promising classes of substances for the above purpose. Yet, none of these substances has been developed as yet to the level of clinical applicability.

PIP: An account is presented of the current uses of interceptively acting substances. Pharmaceuticals used thus far for postcoital contraception (estrogens, gestagens, and combinations of these) are suitable for a single application, but their regular use is limited by side effects. Various approaches are now being taken to develop effective contraceptives for continuous application which have few side effects. Antigestagens, LHRH-analogues, and immunological contraceptives are among the most promising classes of substances for the above purpose, yet none of these has yet achieved a level of clinical applicability. (author's modified)

[Success rates in in vitro fertilization--a mathematical problem? Comments on the article by M. M. Seibel in Obstet. Gynecol. 72 (1988) 265]. / Erfolgsraten bei der In-vitro-Fertilisation--ein mathematisches Problem? Gedanken zum Artikel von M.M. Seibel in Obstet. Gynecol. 72 (1988) 265.

In vitro fertilization, GIFT and related methods have given new perspectives for the treatment of sterility and are applied worldwide. Despite an increasing application of these methods success rates are still relatively low. It may be difficult for sterility patients and their gynecologists to get a clear imagination about the success rates of an IVF-program. This was mentioned in the "Green Journal" by M.M. Seibel, the article of whom has been taken as a basis for some thoughts about the problem. Unclear statements and different bases for reports of success rates may lead to unrealistic expectations concerning the chance for a successful treatment by IVF. Therefore, in discussion with patients only comprehensible figures should be mentioned, e.g. a rate involving numbers of term pregnancies and oocyte retrievals. Taking this as a crucial point the patient and her partner should be informed about their chances depending on their individual findings and the facilities of the sterility centre.

[Lymphography in malignant vulvar and vaginal tumors. 1. Clinical significance]. / Lymphographie bei malignen Vulva- und Vaginatumoren. 1. Klinischer Wert.

The results of a retrograde analysis of lymphographic processes in 111 patients with malign vulvar and vaginal tumours are substantiating statements concerning the importance of lymphography in diagnosing metastastic processes in lymph-nodes of the inguinal and retroperitoneal region. -- Metastases could be proved lymphographically in 24 (34%) out of 70 carcinomas of the vulva and 8 (22%) out of 37 carcinomas of the vagina. In 24% of all patients with carcinomas of the vulva there were lymph-nodes involved, in two of these cases without a simultaneous involvement of the inguinal region. With carcinomas of the vagina a lumbar involvement was found in 50% of the cases. The accuracy of lymphographic diagnosis was 79% regarding the inguinal region and 89% in the iliac region. Despite of the lower accuracy with regard to inguinal lymph-nodes lymphography exceeds findings obtained by clinical palpation in this respect. As a result of the study, the use of lymphography in case of vulvar and vaginal carcinomas of all clinical stages is considered to be profitable for diagnosing and therapy planning.

[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.

[Recent knowledge on follicle and oocyte maturation. 2. Oocyte development and maturation]. / Neuere Erkenntnisse zur Follikel- und Eizellreifung. 2. Mitteilung: Eizellentwicklung und Eizellreifung.

A review is given about the present knowledge in oocyte development and oocyte maturation. The four parts of the review contain: development of the oocyte in the fetal ovary, morphology and metabolism during meiotic arrest, oocyte maturation, and the relations between oocyte maturation and in vitro-fertilization in the human. The morphological and biochemical changes in the maturation process and present hypotheses about maturation regulation are described especially. The increasing knowledge in this field supports the progress of in vitro-fertilization in the human. On the other hand this technique contributes importantly to new directions in oocyte research.

[First experience with an in vitro fertilization program at the Rostock University Clinic of Gynecology and Obstetrics]. / Erste Erfahrungen mit einem In-vitro-Fertilisationsprogramm an der UFK Rostock.

In vitro fertilization as an aid in diagnosis and treatment of the sterile couple has been used at the university clinic of gynecology and obstetrics in Rostock since the beginning of 1983. 17 women were treated in the first series of in vitro-fertilization and embryo transfer in September and October 1983. After treatment with clomiphene and HCG in 16 women one or more oocytes were harvested. In 14 women one or more oocytes were fertilized. Embryo transfer was performed in five cases. No pregnancy resulted. The causes of the low cleavage rate and possibilities for improvement of the results are discussed.

[Comparative light- and electron microscopy findings in oocytes obtained by laparoscopy during the cycle period close to ovulation]. / Vergleich licht- und elektronenmikroskopischer Befunde von laparoskopisch gewonnenen Eizellen aus ovulationsnahen Zyklusabschnitten.

Oocytes recovered by diagnostic laparoscopy can be divided in three categories--atretic, non-ovulatory and pre-ovulatory oocytes. Examples for those three categories are demonstrated. The findings from survey sections and from transmission electron microscopy were used for the retrospective characterization of the light micrographs and the description of the surroundings. Methodic experiences allow further research on oocytes and embryos with developmental defects. Two examples were shown. Our experiments yielded, that the examination with light and electron microscopy is suitable for statement in diagnostic laparoscopies and that these examinations were advantageous for the preparation of an in vitro fertilization program.

[In vitro fertilization and embryo transfer. Personal experiences in the introduction of laboratory methodology]. / In-vitro-Fertilisation und Embryotransfer. Eigene Erfahrungen bei der Einführung der Labormethodik.

Our laboratory technique includes recovery and handling with gametes outside the body, in vitro fertilization, culture of embryos, and finally embryo-transfer. Time-table, culture media and technique of the cultivation as well as laboratory devices are described and than compared with informations about methods from other teams. The necessity of transport of the follicle fluids from operating theatre to laboratory is given caused by local conditions. All dates about number of oocytes (73), quantities of preovulatory oocytes (47) and cleavage rates (55%) are descended from 30 laparoscopic oocyte recoveries of the 2. in vitro fertilization program of the university woman hospital in Rostock, January and February 1984.

[A transportation vehicle for laparoscopically obtained follicular specimens]. / Transportwagen für laparoskopisch gewonnene Follikelpunktate.

Structure, function and first results with a vehicle for transportation were described. This apparatus allows to store laparoscopic harvested follicular fluids for a while in constant temperature and in air condition with 5% CO2 in compressed air. Simultaneously the follicular fluids were transported in this vehicle from operating theatre to the laboratory.

[Psychic attitude of women to irreversible contraception (author's transl)]. / Zur psychischen Verarbeitung der irreversiblen Kontrazeption bei der Frau.

Thirty-four of 100 women who had undergone officially sanctioned irreversible contraception at the Gynaecological Department of Wismar Regional Hospital were selected at random for follow-up investigation, two-and-a-half to one year after the intervention. The following psychological tests were taken: a standardised interview based on abridged psychopathological method, Freiburg personality inventory, record of complaints according to Kasielke, and the multiple-choice vocabulary test according to Lienert. Psychiatric examination was added on the basis of a structured psychopathological record system according to Grünes and Kühne. The following results were obtained from the study: All probands exhibited positive attitudes to the method of irreversible contraception. They said they would choose the same option, if they had to were asked again. They recommended the same decision to other women. Inner conflicts because of the irreversible nature of the intervention, problems of selfvalue, and impairment of partnership relations were not reported. Nor did any of the women wish refertilisation. The gynaecological intervention did in no single case turn out as source for neurotic developments or other psychiatrically relevant symptoms. However, the possibility of neurosis must be reckoned with, as it must with any other medical intervention. This risk may be effectively encountered by due consideration of the patient's personality, clarified indication, adequate information, and therapeutic support for the patient's effort to get to grips with the psychic problem. Hence, irreversible contraception can be an alternative, also for its psychic consequences, for women above 35 to whom safe reversible contraceptives cannot be applied for whatever reasons, although they have completed their own family planning.

PIP: 34 of 100 women who had undergone officially sanctioned sterilization at the Gynecological Dept. of Wismar Regional Hospital were selected at random for a follow-up investigation 1-2 1/2 years after the intervention. The following psychological tests were taken: standardized interview based on abridged psychopathological method, Freiburg personal interventory, record of complaints according to Kasielke, and the multiple choice vocabulary test according to Lienert. Psychiatric examination was added on the basis of a structured psychopathological record system according to Grunes and Kuhne. The following results were obtained from the study. All subjects exhibited positive attitudes to the method of sterilization. They said they would select the same option if they were asked again and they recommened the same decision to other women. Inner conflicts due to the irreversible nature of the intervention, problems of self-worth, and impairment of the partner relations were not reported. Nor did any of the women desire refertilization. The gynecological intervention did in no 1 case result in neurotic developments or in any other psychiatrically relevant symptoms. However, the possibility of neurosis must be reckoned with, as it must with any medical intervention. Risk may be effectively encountered by due consideration of the patient's personality, clarified indication, adequate information, and therapeutic support for the patient's efforts to come to grips with the psychological problem. Thus sterilization can be an alternative for women over age 35 for whom reversible contraception is contraindicated, despite the completion of desired family size. (author's)