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Biomedical subjects

L Hamberger

Publications and source records attributed to L Hamberger.

At least 73 records · Page 4Linked to original sources

Simplification of IVF: minimal monitoring and the use of subcutaneous highly purified FSH administration for ovulation induction.

During the past few years much effort has been put into simplifying the clinical management of in-vitro fertilization/embryo transfer cycles. One important step was the introduction of transvaginal ultrasound-guided oocyte collection, as previously described. This study describes further simplifications of the clinical management of ovarian stimulation. During the period 1st January 1991 to 31st August 1993, three major simplification steps were introduced. All cycles were down-regulated with a gonadotrophin-releasing hormone (GnRH) agonist according to a long protocol permitting fairly precise programming of the oocyte collection. During period I (n = 329 cycles), closer monitoring by several pelvic ultrasound scans and serum oestradiol was used for monitoring the ovarian stimulation. During period II (n = 230 cycles), only one ultrasound scan was used for monitoring the ovarian cycle; oocyte collections during weekends were avoided. During period III (n = 386 cycles), further simplification of the clinical management was introduced by using a highly purified follicle stimulating hormone (FSH) (Fertinorm/Metrodin HP), which was self-administered s.c. for ovarian stimulation. The take-home baby rates per started cycle for periods I, II and III were 16.4, 32.6 and 31.3% respectively. These figures indicate that when using long down-regulation with a GnRH agonist, simplification of the monitoring of the ovarian stimulation is possible without decreasing the pregnancy rate. Furthermore, the use of a highly purified FSH, self-administered s.c., greatly simplified treatment without compromising cycle outcome or increasing the risk of developing an ovarian hyperstimulation syndrome.

Adult↗

Isolation and culture of human endometrial cells in a three-dimensional culture system.

A cell culture system was established in which endometrial stromal cells were embedded in a collagen matrix and separated from the endometrial epithelium by basement membrane material (Matrigel). The epithelium, seeded on top of the collagen matrix, grew in a monolayer. The cultures were evaluated by light microscopy and transmission and scanning electron microscopy. Light and transmission electron microscopy indicated a polarized columnar epithelium in monolayer with basally positioned nuclei. Scanning electron microscopy revealed a confluent epithelium with an abundance of microvilli and cilia, as well as pinopodes on the apical surface. Immunohistochemical staining for cytokeratin confirmed the epithelial origin of the surface cells, and staining for human collagen IV demonstrated its presence underneath the epithelial cells. This culture system represents a three-dimensional system that imitates the normal endometrium.

Biocompatible Materials↗

Adjuvant growth hormone treatment during in vitro fertilization: a randomized, placebo-controlled study.

OBJECTIVES: To explore the effect of recombinant, human GH on follicular development and oocyte retrieval after gonadotropin stimulation with the addition of GH or placebo to a standard IVF treatment regimen. Further, to investigate whether GH is a more effective adjuvant if the standard treatment regimen is preceded by GH injections. DESIGN: A randomized, double-blind, parallel, placebo-controlled study. SETTING: The IVF unit at university hospital. PATIENTS: Forty normally ovulating women, age 25 to 38 years, with infertility because of tubal factors and being classified as "poor responders" with at least two previously performed and failed IVF attempts. INTERVENTIONS: Human, recombinant GH (Genotropin, Kabi Pharmacia, Uppsala, Sweden) or placebo (0.1 IU/kg body weight per day) was given SC as pretreatment during down regulation with GnRH and during stimulation with hMG according to the randomized protocol. MAIN OUTCOME MEASURES: Number of oocytes retrieved after stimulation, total amount of gonadotropin used, time required for stimulation, number of follicles developing, rate of fertilization, and cleavage in vitro. Further, the quality of embryos, development of the endometrium, rate of clinical pregnancy, and serum and follicular fluid (FF) concentrations of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 were estimated. RESULTS: The number of oocytes retrieved did not differ significantly between the groups, nor did the amount of hMG required for stimulation. The fertilization rate increased in patients who had received GH. Growth hormone caused a significant increase in serum and FF levels of IGF-I. An increase in serum IGFBP-3 could also be recorded in patients who had received GH. CONCLUSION: Although certain beneficial effects were noted in GH-treated patients, the overall results did not support GH as a clinically useful adjuvant treatment.

Adjuvants, Pharmaceutic↗

Fertilization and pregnancy after intracytoplasmic microinjection of acrosomeless spermatozoa.

Spermatozoa lacking acrosomes were injected into the cytoplasm of mature human oocytes. In two subsequent cycles, 12 of 28 (43%) oocytes were fertilized, and the ET of the second cycle resulted in a twin pregnancy. This report describes, to the best of our knowledge, the first case of successful fertilization and delivery after using acrosomeless spermatozoa. Our hope is that with increasing experience with microinjection, in the near future, this type of infertility will not remain a serious problem.

Acrosome↗

Culture of human spare preembryos: association between blastocyst formation and pregnancy.

The rate of blastocyst development was studied in cultures of human fertilized eggs. A total of 195 spare embryos from 86 cycles in 73 in vitro fertilization (IVF) patients resulted in a total of 77 expanded blastocysts, corresponding to an overall blastocyst development of 39%. In the group of patients where pregnancy occurred, at least one of the spare embryos developed into the blastocyst stage in 100% of the patients, while the corresponding figure for nonpregnant patients was 53%. Superficially these results seem to indicate that blastocyst development could be of decisive importance for the success rate in IVF. A detailed analysis revealed, however, that this is not the case as long as in vitro culture before replacement is limited to 2-3 days.

Adult↗

Is the contraceptive effect of 300 micrograms of norethisterone mainly peripheral or central?

The effect of norethisterone (NET) on pituitary function was evaluated by measuring circulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) during the mid follicular phase as well as before and after removal of the corpus luteum (CL) in 30 untreated women and 43 women treated with 300 micrograms of NET daily for three months. All untreated women exhibited significantly elevated FSH levels after removal of the CL irrespective of the stage of the luteal phase. In the NET-treated women, the levels of FSH were significantly raised in women with luteal activity but these levels were not influenced by the operative procedure in those women without luteal activity. The LH levels remained unchanged after removal of the CL in both untreated and NET-treated women. The results suggest that a low dose of gestagen exerts variable effects on pituitary function. The main contraceptive effect seems to be through direct interference with ovarian function.

Adult↗

Intrauterine capsules for incubation of gametes and subsequent release of embryos.

In order to obtain incubation in uteri of spermatozoa, oocytes, and embryos, for treatment of patients referred for in vitro fertilization, a capsule was produced which could contain the human gametes and allow human fertilization and embryo growth after intrauterine introduction. Agar was chosen for capsule material and a mold was constructed for the production of capsules. The material was tested in vitro using mouse embryos and human oocytes and sperm. Intrauterine resolution was tested on mice and by insertion on 11 women. Empty capsules were inserted into the uterine cavity in 15 cycles the day after the luteinizing hormone peak and followed by daily ultrasound examinations. The resolution time was adjusted by changing the wall thickness of the capsules. The final type was dissolved after 3 to 4 days. No complications were observed and capsules could be inserted on all occasions. The major problem was expelling of capsules, which occurred in seven cycles. The problem seemed to be solved by the administration of indomethacin at the day of insertion.

Adult↗

Comparative morphometric study of the endometrium, the fallopian tube, and the corpus luteum during the postovulatory phase in normally menstruating women.

OBJECTIVE: To compare function and histologic structure of the corpus luteum (CL) to the morphology of the endometrium and the fallopian tube in normally menstruating women. DESIGN: Circulating steroid and luteinizing hormone (LH) levels were compared with CL steroid production in vitro and the histology of CL, endometrium, and the fallopian tube at four stages of the postovulatory phase (days LH +/- 0/LH+3, LH+4/LH+7, LH+8/LH+11, LH+12/onset of menstruation). SETTING OF PATIENTS: The study included 28 volunteers with proven fertility undergoing surgical sterilization timed in relation to the LH surge. INTERVENTIONS: Blood and urine samples for LH, progesterone (P), and estradiol assessment were obtained before (simultaneously with ultrasound examinations), during, and after operation. Biopsy specimens from CL, endometrium, and fallopian tube were taken at the surgical sterilization and subjected to morphometric analyses. MAIN OUTCOME MEASURES AND RESULTS: Significant correlation was found between the endometrial dating and the LH surge (r = 0.923) and between the dating of the endometrial and CL biopsies (r = 0.918). A significant correlation (P less than 0.01) existed between circulating P levels and two endometrial indices; the number of vacuolated cells (LH+4/LH+7) and the glandular diameter (LH+8/LH+11). CONCLUSION: In normally menstruating women, the endometrial biopsy is likely to closely gauge the CL activity provided the biopsy is timed in relation to the LH surge.

Adult↗

[Mammography and sonography in the diagnosis of recurrence after breast-preserving therapy of breast carcinoma].

89 patients, who underwent conservative surgery for breast cancer were followed up with mammography and real-time sonography. 78 patients underwent postoperative irradiation. Depending on the time interval between irradiation and examination various alterations in mammographic and sonographic patterns were evident. Of 14 biopsy-confirmed local recurrences, 11 were diagnosed by mammography and 12 by sonography. Sonography was superior in the diagnosis of small recurrences in breasts with radiation-induced increased density, whereas mammography showed better results in the detection of tumours with microcalcifications. As a result of the different sonographic aspect of recurrent tumours and scar tissue, the number of false positive diagnoses of sonography was markedly lower compared to that of mammography (2 versus 18). Combined use of mammography and sonography should therefore lead to better results in the diagnosis of local recurrences and to a reduction of unnecessary biopsies.

Adult↗

In-vitro synthesis of steroid hormones in corpora lutea from normal women and women treated with 300 micrograms norethisterone.

The in-vitro oestradiol (E2) and progesterone (P) production by corpora lutea (CL) obtained at sterilization from 30 untreated women and 43 women treated with norethisterone (NET) 300 micrograms daily was measured. The CL were obtained at different stages of the luteal phase in the untreated women [luteinizing hormone (LH) 0 to +3, n = 7; LH +4 to +7, n = 7; LH +8 to +11, n = 9; LH +12 to menses, n = 7] and on days LH +8 to +11 or cycle days 22 to 26 in the NET-treated women. In the treated women, four types of ovarian reaction were identified. Four women showed ovarian reaction Type A (completely inhibited ovarian activity), 14 women Type B (marked follicular activity, but no luteal function), 12 women Type C (normal follicular activity, followed by insufficient luteal function) and 13 women Type D (apparently normal follicular and luteal activity). The CL were incubated in Eagle's medium with and without stimulation by human chorionic gonadotrophin (HCG) for 2 and 4 h. In the untreated women, P and E2 production increased significantly with both incubation time and stimulation by HCG throughout the luteal phase, except in the late luteal phase (LH +12 to menses) where P increased (P less than 0.01) only after 4 h stimulation by HCG. The maximal production of P was found after 4 h incubation with HCG stimulation of CL tissue in the early-mid luteal phase (LH +4 to +7).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Peritoneal fluid volume and levels of steroid hormones and gonadotrophins in peritoneal fluid of normal and norethisterone-treated women.

Peritoneal fluid and blood samples were collected at surgical sterilization from 30 untreated women at various stages of the luteal phase and from 43 women treated with 300 micrograms norethisterone daily. Levels of oestradiol, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured. The highest peritoneal fluid volume (mean, 23.1 ml) was found in the early luteal phase (LH 0 to + 3) and the lowest (mean, 5.9 ml) in the late luteal phase (LH + 12 to menses). The norethisterone treatment diminished the formation of peritoneal fluid and the degree of inhibition was dependent upon the type of ovarian reaction to norethisterone. Progesterone and oestradiol levels were higher in peritoneal fluid compared to plasma throughout the luteal phase and during norethisterone treatment. A comparison of the levels of these steroids between untreated controls (LH + 8 to + 11) and norethisterone-treated women demonstrated that the progesterone levels in peritoneal fluid were highly reduced by norethisterone treatment, while the oestradiol levels were not affected. The FSH and LH levels were, in contrast to the steroid hormones, significantly lower in peritoneal fluid than in plasma, both in the untreated and the treated women. No differences in the FSH or LH levels between the untreated and treated women were found. The results indicate that the peritoneal fluid volume and the steroid hormone levels in peritoneal fluid vary with the stages of the luteal phase. Norethisterone treatment significantly reduced the peritoneal fluid volume as well as its progesterone concentration, whereas the oestradiol and gonadotrophin levels remained unchanged.

Adult↗

Prostaglandin-E2 released by pre-implantation human conceptuses.

This work investigates the production of prostaglandin E2 (PGE2), a well known modulator for the suppression of immune cells, by pre-implantation human conceptuses from the 4-cell stage to the hatched blastocyst and by cumulus oophorus cells, these being obtained from an IVF/ET program. Cumulus cell complexes cultured for 48 h produced considerable amounts of PGE2, necessitating complete removal of their influence on the conceptus cultures. All stages of the human conceptus studied produced PGE2 during 48-h cultures, the greatest amounts from late blastocysts, and from those cultured in media containing bovine serum albumin rather than human donor serum. Indomethacin-treated control blastocysts confirmed the synthesis and release from the human conceptuses. The production of PGF2a from human blastocysts could not be demonstrated.

Blastocyst↗

Human gonadotrophins.

Treatment with exogenous gonadotrophic hormones to overcome certain cases of female infertility has been used for more than 30 years. Children born after such treatment have not shown any increased incidence of abnormalities (genetic or otherwise) and their reproductive ability seems normal. Furthermore, no increase in malignant disease (breast, ovarian, endometrial) have been reported following such repetitive gonadotrophic stimulations. Thus it seems the treatment can be regarded as safe. Two categories of patients are treated today. Firstly, hypothalamic-hypophyseal insufficiencies (WHO group I), where treatment is compulsory for attaining fertility, and secondly (including anovulation WHO group II), more or less regularly cycling women, where gonadotrophic treatment is used to augment fertility. Especially in the latter group, caution must be taken not to induce adverse effects. To meet these demands, exogenous gonadotrophic stimulation needs to be combined with other drugs and regimens that take into consideration the problems created by the concomitant presence of endogenous gonadotrophins.

Anovulation↗

Luteotropic effects of prostaglandins I2 and D2 on isolated human corpora luteum.

Human corpora lutea (CL) of the menstrual cycle or early pregnancy were excised at operation, cut into pieces, and incubated in the presence of human chorionic gonadotropin or prostaglandin (PG) I2 and D2. After incubation, the tissue levels of 3',5' cyclic adenosine monophosphate (cAMP) and the medium concentration of progesterone (P) was determined. Prostaglandin I2 and PGD2 stimulated cAMP production in the CL of both the menstrual cycle and early pregnancy. This stimulatory effect was maximal for PGI2 after 5 minutes and for PGD2 after 10 minutes. Repeated addition of the PGs during 120 minutes in the CL from the menstrual cycle resulted in a persistent cAMP elevation and stimulated P formation. The stimulatory effects of PGI2 and PGD2 on cAMP and P production in vitro indicate that these local hormones play a role in the normal development of human menstrual CL and in the persistence of the CL of early pregnancy.

Corpus Luteum↗