A study was performed in order to investigate the participation of prostaglandins (PGs) during implantation. The effects of indomethacin on mouse blastocyst attachment and trophoblastic outgrowth were examined in vitro. Studies were also carried out on cultures supplemented with PGE2 and/or PGF2 alpha along with indomethacin. (1) Blastocyst attachment and trophoblastic outgrowth were inhibited by indomethacin dose-dependency. (2) In the cultures supplemented with indomethacin and PGE2 or PGF2 alpha, respectively, the inhibitory effects of indomethacin were reduced. (3) In the cultures supplemented with all three substances with treatment (1) and (2), inhibition of indomethacin was partially reversed, but still lower than control group without indomethacin. The above results indicate that both PGE2 and PGF2 alpha have a promoting effect on implantation, and PGF2 alpha was more effective than PGE2.

Animals↗

PubMed1989

Significance of oestradiol values in IVF-ET under a combined GnRH analogue--desensitization and simultaneous gonadotrophin stimulation for the outcome of pregnancies.

The present study was undertaken to determine the relationship between the actual value of oestradiol (E2) levels at the time of human chorionic gonadotrophin (HCG) administration and 36 h later at follicular puncture in in-vitro fertilization and embryo replacement (IVF-ET) patients and the resulting pregnancy rates. Between January and May 1988, 94 patients underwent follicular recruitment with various types of human menopausal gonadotrophin (HMG), follicle stimulating hormone (FSH) and HCG stimulation protocols. E2 and luteinizing hormone (LH) measurements were taken daily beginning on day 2 of the cycle. After an initial sonographic scan at the beginning of the treatment, vaginal sonographic follicular studies were performed based on the associated oestradiol levels from approximately day 8 of the cycle on. Four findings resulted: (i) When follicles reached a diameter of greater than 1.5 cm, the aspirated oocytes were at all stages of maturity. One can rely on follicular diameters alone if the patients' previous cycles and their E2 responses are known. (ii) A minimum plasma level of greater than 800 pg of E2 on the day of administration of HCG is predictive of a favourable pregnancy success rate per embryo transfer. Oestradiol levels do not, however, directly correlate with oocyte maturity and embryonic growth. (iii) The pregnancy rates in the low responding group when compared to the medium and high responding groups were statistically significantly lower despite replacement of an equivalent number of oocytes and cleaving embryos. (iv) We hypothesize that the responsiveness of the endometrium depends on adequate stimulation with oestradiol which it does not receive in the low responders.

Chorionic Gonadotropin↗

PubMed1989

Results of the use of a pure urinary FSH stimulation regime in patients unsuccessfully treated with hMG in an in vitro fertilization program.

63 infertile patients who failed in achieving pregnancy for several cycles with human menopausal gonadotropin stimulation protocol in our in vitro fertilization program were subsequently treated with urinary FSH regime. In 25 of these patients, the leading diagnosis was an elevated basal LH/FSH ratio (i.e. above 2), 29 women had an irreparable tubal factor, 9 patients had endometriosis, and 21 couples suffered from an additional male factor. The FSH stimulation protocol was initiated on day 2 of the cycle, the highest doses were given on the first days and reduced thereafter. Hormone measurements concerning estradiol and LH were started on day 2 of the cycle, ultrasonic evaluation on day 7 of the cycle. After 48 pelviscopic follicle punctures and 39 embryotransfers 12 cases resulted in clinical pregnancies. One case terminated in a miscarriage and 2 pregnancies were of ectopic location.

Adult↗

PubMed1989

[Modification of the penetration rate of human spermatozoa in the zona pellucida free hamster oocyte system by the use of polyclonal and monoclonal antibodies to human sperm].

Incubation of human spermatozoa with polyclonal anti-sperm antibodies from sterile females reduced the penetration rates in the zona-pellucida-free hamsteroocyte assay significantly. Twelve sera having titers from 1:4,096 to 1:64 were used. Fifty-three ejaculates from men with normozoospermia were tested. A few of the ejaculates used were classified as slightly pathological showing asthenospermia. At an average titer 1:860 the reduction of penetration rate was about 49% (range 9-90%). The degree of reduction was dependent on the agglutination titer of the test serum, the presence of immobilizing antibodies, the amount of antiserum added, and on the quality of the ejaculates to a minor extent. The penetration rate of human spermatozoa in zona-pellucida-free hamster-oocytes was reduced by 4 monoclonal anti-sperm-antibodies (A-24, B-20, III,3, and VII-5) out of 6 tested. The other 2 (VI-1 and VI-16) left the penetration rates virtually unchanged. The extent of penetration rate reduction depended on the concentrations of antibodies A-24, B-20, III-3, and VII-5; if undiluted, they produced a significant reduction of penetration rates, the largest average reduction being almost 50% with undiluted antibody A-24. Decreasing concentrations of the monoclonal anti-sperm-antibodies resulted in significantly smaller reductions of sperm penetration rates. The reason for the reduced penetration rates observed may be a blockage of receptors on the sperm surface by the named monoclonal anti-sperm-antibodies. This can inhibit enzyme reactions of the spermatozoa, or interfere with the interaction between oocyte and spermatozoa membranes. It is noted that only the antibody III-3 caused agglutination of human spermatozoa in the micro-sperm-agglutination and immobilization test. Therefore, the agglutination or immobilization of spermatozoa may not be held responsible for the reduced penetration rates after addition of monoclonal antibodies, as opposed to the findings with polyclonal antibodies.

Antibodies↗

PubMed1989

Pathogenesis, diagnosis and treatment of genital endometriosis.

The etiology of genital endometriosis remains unclear, but it is evident that persisting endometriotic foci are stimulated by ovarian steroid hormones. Many cases are treated by surgery either via laparotomy or pelviscopy. Endocrine treatments with testosterone, gestagens, danazol and gestrinone have also been used to some effect. Recently developed analogs of gonadotropin-releasing hormone (GnRH) have demonstrated the high binding capacities of receptors involved in the down-regulation of the normal cycle which result in atrophy of the endometrium. These agents could therefore be used in the treatment of endometriosis. To date, 924 patients with pelvic endometriosis have been treated in our department with conventional endocrine therapies, 40 patients were treated with buserelin (D-Ser (Bu)6 luteinizing hormone-releasing hormone monopeptide-ethylamide), 900 micrograms/day intranasally, and 50 patients with goserelin depot, a GnRH analog of D-Ser (Bu)6- Azegly10-GnRH, with depot applications (3.6 mg per 4 weeks). The stage of development of endometriosis was determined using the endoscopic endometriosis classification prior to and after endocrine treatment. A complete check of the pelvis was carried out each time and a careful revision of the endometriotic foci undertaken. Endocrine treatment of endometriosis allowed 60% of previously sterile patients to become pregnant. Ovarian function in these patients was normal. The analogs proved to be clinically effective, safe and were well tolerated. Gestrinone proved to be the endocrine treatment of preference.

Endometriosis↗

PubMed1988

Comparison of human menopausal gonadotropin administered once and twice daily in an in vitro fertilization and embryo transfer program.

This is a retrospective study which evaluates the use of twice-daily (BID) human menopausal gonadotropin (hMG) for follicular stimulation in an in vitro fertilization and embryo transfer (IVF-ET) program from February to June 1985 and compares it to daily (QD) hMG from August to December 1984. All QD patients were begun on 2 ampoules of hMG, and BID patients on 2 ampoules twice daily. Individual patient responses to hMG determined subsequent doses so as to achieve continuously rising estradiol levels. The BID stimulation scheme appears to increase statistically characteristics that would be present in the ideal stimulated cycle such as elevated follicular-phase estradiol (E2) (2125 pg/ml for the BID vs 1581 pg/ml for the QD group) with an increase in the number of patients achieving the "desired" Jones pattern, increased oocyte retrieval (4.01 vs 2.45), and an increase in the number of transferred concepti (2.69 vs 1.87). No statistical differences were noted in the number of endogenous luteinizing hormone (LH) surges or mean LH. The luteal phase does not appear to have been altered by the frequency of administration. Although the increase in the total (20.0 vs 14.5%) and live-born/ongoing (16.9 vs 11.8%) pregnancy rate per laparoscopy with the BID regimen is not statistically significant, it may be that it is clinically relevant.

Drug Administration Schedule↗

PubMed1988

Ovulation induction for in-vitro-fertilization and embryo transfer applying decapeptyl (DTRP-6 LH/RH) in combination with HMG or FSH.

47 patients out of the IVF-program of the Department of Obstetrics and Gynecology University of Kiel, who demonstrated in previous stimulation cycles premature LH surges, were treated in two modalities with a down regulation applying the GnRN-analogue decapeptyl (DTRP-6 LH/RH) and a concomitant HMG- or FSH-stimulation. The down-regulation was started after ovulation up to a negative LH/RH test followed by a concomitant gonadotropin stimulation in group 1. In group 2 a parallel treatment with decapeptyl and HMG or FSH was performed from day 2 of the cycle. 10 husbands of the punctured patients had pathological sperm. In both groups 6 patients were discarded from of the stimulation protocol as their oestradiol responses were not adequate, sperm contamination was detected late in one case, and in one patient a premature LH surge occurred once again. In 36 patients vaginal follicular punctures were performed. With respect to pregnancies group 1 revealed a much higher pregnancy rate than group 2. It seemed better to start the down-regulation with the GnRH-analogue decapeptyl in the luteal phase of the previous cycle. The treatment with decapeptyl should not only be applied in patients with previous LH surges but also in order to establish a synchronous follicular maturation in ovulating patients treated for in-vitro fertilization, or gamete-intra-Falloppian-tube-transfer.

Adult↗

PubMed1988

Local infiltration of ornithine 8-vasopressin (POR 8) as a vasoconstrictive agent in surgical pelviscopy (applied to myoma enucleation, salpingotomy in cases of tubal pregnancy and peripheral salpingostomy).

For better hemostasis in cases of operative pelviscopy in 60 patients Ornithine-8 Pitressin (POR 8) was applied locally as a vasoconstrictive agent in quantities of up to 50 ml at a concentration of 0.05 IU/ml. From the broad spectrum of indications for operative pelviscopy, the following procedures employing local application of a 5% POR 8 solution to produce intraoperative ischemia are described: Myoma enucleation, longitudinal salpingotomy with conception product extraction in the conservative treatment of a tubal pregnancy, ovarian cystectomy and salpingostomy. The tolerance was optimal no side effects were observed.

Endoscopy↗

PubMed1988

[Microinjection of spermatozoa into the oocyte. An experimental model for assisted conjugation in oligo-asthenozoospermia as a cause of sterility].

This study investigates the possibilities to treat oligo-asthenozoospermia, a cause of sterility, by assisted conjugation. After completing acrosome reaction, normal motile spermatozoa are microinjected into mouse oocytes. After 2 hours of incubation time in medium with lactate and albumins, spermatozoa are put into dibutyryl 3',5'-guanosine monophosphate (dbcGMP) and imidazole for the completion of an acrosome reaction. One motile spermatozoon each was injected microsurgically into the perivitelline space of an oocyte. The survival rate of the oocytes after injection was around 85%. The oocytes with two pronuclei and a second polar body were considered as fertilized. Of those injected oocytes 21.5% were fertilized with acrosome reacted spermatozoa, whereas only 5.6% were fertilized with spermatozoa without dbcGMP treatment. Thus, motile and acrosome reacted spermatozoa essentially fertilize oocytes at microinjection into the perivitelline space very well. This technique may become a hopeful procedure to treat human oligo-asthenozoospermia in an IVF/ET-programme.

Animals↗

PubMed1988

Fertilization through spermatozoal microinjection: significance of acrosome reaction.

Acrosome-reacted spermatozoa were microinjected into the perivitelline space of mouse oocytes. After 2 h incubation in culture medium containing lactate and albumin, spermatozoa were transferred into culture medium containing 12 mM of dibutyryl cyclic guanosine 3',5'-monophosphate (dbcGMP) and 10 mM imidazole for 20 min. One motile spermatozoon was injected into the perivitelline space of each oocyte. Fertilization was recognized by the presence of a second polar body and two pronuclei. The overall fertilization rate was 19.6% in the case of dbcGMP-treated spermatozoa as compared to 5.3% for non-treated spermatozoa. Thus, acrosome-reacted motile spermatozoa improve the fertilization rate of sperm microinjection. Sperm microinjection may be a method to foster fertility in cases of oligo-/asthenozoospermia in human in-vitro fertilization.

Acrosome↗

PubMed1988

Microinjection of spermatozoa into oocytes.

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Animals↗

PubMed1987

Estradiol values under gonadotropin stimulation in relation to the outcome of pregnancies in in vitro fertilization and embryo transfer.

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Adult↗

PubMed1987

[Comparison of microscopic and pelviscopic tubal surgery].

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Endoscopy↗

PubMed1987

[Effect of maternal age on the success rate of in vitro fertilization. A comparison of human and animal experiment data].

From January 1981 to September 1986 863 patients have been treated by the technique of in vitro fertilization (IVF) at the department of Obstetrics and Gynaecology, University of Kiel. The classification of all patients in four different age groups reveals the fact, that there is no influence of maternal age on the number of patients having a follicular puncture. The rate of oocytes, fertilizations, and transfers is the same as well. Contrary to these findings there is a significant correlation between the age of a woman and the pregnancy rate after IVF. Women under 30 years of age have a pregnancy rate of 25.4% per transfer. This amount decreases to 17.7% in women of the age group 31 to 35 and further on to 9.7% in women between 36 and 40. Up till now, not one patient above the age of 40 has become pregnant after IVF at the University Clinic in Kiel. Therefore this technique is not recommended for patients above the age of 40.

Animals↗