Follicular fluid hormone concentrations after ovarian stimulation using gonadotropin preparations with different FSH/LH ratios. I. Comparison of an FSH-dominant and a purified FSH preparation.

OBJECTIVE: A small amount of LH is necessary for 17beta-estradiol production in the ovarian follicle. Human menopausal gonadotropin (hMG) contains equal amounts of FSH and LH activity, whereas recombinant FSH is a gonadotropin preparation without LH. The aim of the present randomized study was to investigate whether ovarian stimulation treatment with recombinant FSH or hMG resulted in different steroidal composition of follicular fluid. METHODS: Antral fluid from mature follicles was collected in in vitro fertilization cycles and concentrations of testosterone, androstenedione, estrone, estradiol, progesterone, FSH, and LH were determined. Seven patients (27 samples) were treated with hMG, 6 patients (22 samples) with recombinant FSH. RESULTS: Androgen, estrogen, progesterone, and FSH concentrations in follicular fluid tended to be lower in the group treated with recombinant FSH, but the variation was large and differences were statistically not significant. CONCLUSION: Treatment with a gonadotropin preparation containing no LH resulted in adequate androgen and estrogen levels in antral fluid of the ovarian follicle in women with normal endocrine profiles, even during pituitary suppression by a GnRH agonist. Apparently, the amount of endogenous LH was sufficient for steroid production within the follicle.

Follicular fluid hormone concentrations during controlled ovarian hyperstimulation using gonadotropin preparations with different FSH/LH ratios. I. Comparison of an FSH-dominant and a purified FSH preparation.

OBJECTIVE: The aim of the present randomized study was to investigate whether ovarian stimulation treatment with gonadotropin preparations containing different amounts of LH activity resulted in variations of steroidal composition of follicular fluid. A different endocrine milieu within the follicle might influence oocyte quality. METHODS: Antral fluid from mature follicles was collected in in vitro fertilization cycles and concentrations of testosterone, androstenedione, estrone, estradiol, progesterone, FSH, and LH were determined. A comparison was made between treatment with a purified FSH preparation (nine patients, 35 follicular fluid samples) and a FSH-dominant human menopausal gonadotropin (hMG) preparation (nine patients, 34 samples). RESULTS: No differences in any of the hormone levels could be detected between the two groups. CONCLUSION: Treatment with gonadotropin preparations containing different FSH/LH ratios did not result in different androgen, estrogen and progesterone levels in follicular fluid.

Follicular fluid hormone concentrations after ovarian stimulation using gonadotropin preparations with different FSH/LH ratios. II. Comparison of hMG and recombinant FSH.

OBJECTIVE: A small amount of LH is necessary for 17 beta-estradiol production in the ovarian follicle. Human menopausal gonadotropin (hMG) contains equal amounts of FSH and LH activity, whereas recombinant FSH is a gonadotropin preparation without LH. The aim of the present randomized study was to investigate whether ovarian stimulation treatment with recombinant FSH or hMG resulted in different steroidal composition of follicular fluid. METHODS: Antral fluid from mature follicles was collected in in vitro fertilization cycles and concentrations of testosterone, androstenedione, estrone, estradiol, progesterone, FSH, and LH were determined. Seven patients (27 samples) were treated with hMG, 6 patients (22 samples) with recombinant FSH. RESULTS: Androgen, estrogen, progesterone, and FSH concentrations in follicular fluid tended to be lower in the group treated with recombinant FSH, but the variation was large and differences were statistically not significant. CONCLUSION: Treatment with a gonadotropin preparation containing no LH resulted in adequate androgen and estrogen levels in antral fluid of the ovarian follicle in women with normal endocrine profiles, even during pituitary suppression by a GnRH agonist. Apparently, the amount of endogenous LH was sufficient for steroid production within the follicle.

Serum levels of follicle-stimulating hormone and luteinizing hormone after subcutaneous administration of human menopausal gonadotropin during pituitary suppression.

OBJECTIVE: The present study investigated the pharmacokinetics of a single subcutaneous dose of human menopausal gonadotropin (hMG) on serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations. SUBJECTS AND METHODS: Six healthy female volunteers, aged 20-40 years, with regular menstrual cycles and normal endocrine profiles, who were not receiving any hormonal medication, were treated with the gonadotropin-releasing-hormone agonist buserelin to suppress endogenous gonadotropin release. One volunteer dropped out during treatment. When the serum estradiol concentration had fallen to below 500 pmol/L, an injection of 150 IU hMG (HumegonR) was given subcutaneously. Immediately before injection and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 15, 20, 24, 48 and 96 hours after, blood samples were drawn for determination of FSH and LH concentrations. RESULTS: The baseline FSH level was 2.8 IU/L, and peak concentration (6.8 IU/L) was reached 12 hours after hMG injection (median values). Exogenous LH could not be measured because of the presence of endogenous LH. DISCUSSION: The pattern of serum FSH concentrations after a single injection of hMG was found to resemble that seen after intramuscular hMG administration, although the peak FSH value was reached somewhat later.

Hormonal serum profiles and follicular development after intramuscular and pulsatile intravenous administration of human menopausal gonadotrophin.

A study was performed to compare, in a randomized way, the effect of pulsatile intravenous (i.v.) and intramuscular (im) human menopausal gonadotrophin (hMG) administration on hormonal serum profiles and follicular development in in vitro fertilization (IVF). Fourteen IVF patients participated in the study, aged between 20 and 40 years, with a normal endocrine profile, no hormonal medication used for at least 3 months previously, no endometriosis, both ovaries present and a normal male factor. Seven patients were treated with im hMG at a daily dose of 150 IU and seven patients with pulsatile i.v. hMG at a daily dose of 112.5 IU, in both cases in combination with buserelin. Ultrasonography was performed every other day during the stimulation phase and blood samples were collected once daily up to five times a day during the entire IVF cycle. Serum concentrations of follicle-stimulating hormone, luteinizing hormone, 17 beta-oestradiol, progesterone and human chorionic gonadotrophin were determined. There were no differences in hormonal profiles between the two groups. The numbers of retrieved oocytes, fertilization rates and mean embryo quality were identical in this study, as was follicular growth. In conclusion, in the present randomized study no differences were observed in hormonal levels or follicular development after im and pulsatile i.v. hMG treatment.

Patterns of serum FSH, LH and hCG after i.m. or i.v. administration of hMG during pituitary suppression.

OBJECTIVE -- The study was undertaken to investigate the effects of a commonly used ovarian stimulation regimen on gonadotropin levels. METHODS -- The behavior of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG) was studied after intramuscular (i.m.) and intravenous (i.v.) human menopausal gonadotropin (hMG) administration. Six female volunteers participated in the study. During pituitary suppression with a gonadotropin-releasing hormone (GnRH) agonist (Buserelin), a single dose of hMG (150 IU) was injected i.m. or i.v., in a cross-over design with an interval of 2 weeks. Blood samples were collected frequently after the injection. Serum concentrations of FSH, specific LH and hCG were determined. RESULTS -- After i.m. administration of hMG, a peak FSH concentration of 7.4 +/- 1.3 U/L was reached after 8 (6-24) hours, with a subsequent decrease. At 0.5 hour after i.v. administration, peak FSH values of 30.5 +/- 5.6 U/L were obtained, followed by a decrease to baseline levels within 48 hours. Exogenous LH and hCG were hardly detectable after i.m. administration of hMG. One-half hour after i.v. injection of hMG, a small increase in specific LH levels to 6.7 +/- 2.6 U/L was shown, followed by a decline. hCG concentrations increased after i.v. hMG administration to 7.6 +/- 1.6 U/L.

Sperm functional changes and fertilization in vitro in co-culture with human skin fibroblasts.

This study was undertaken to evaluate the effects of human skin fibroblast monolayers on human sperm function and fertilization in vitro. Sperm function was evaluated using the hamster oocyte penetration assay (HOPA) and zona binding assay (ZBA) in medium alone and in co-culture with human skin fibroblast monolayers and suspensions. The ZBA was also studied in fibroblast conditioned medium and in bovine oviduct cell monolayers and suspensions. Fertilization was measured both in in-vitro fertilization (IVF) couples with a normal semen analysis (first study; randomized) and in IVF couples with subnormal semen analysis (second study; each patient served as its own control). The HOPA results were not significantly different with or without fibroblasts. In all co-culture situations and in conditioned medium the ZBA scored significantly lower than medium alone. No significant differences with respect to IVF were observed between the co-culture and the control group in either study. The mean fertilization rate per patient was approximately 60% in the group with normal semen analysis and approximately 25% in the group with abnormal semen analysis. From this study we conclude that although co-culture with human skin fibroblasts and epithelial cells influences the results of some sperm function tests, it does not influence fertilization in vitro.

Human serum and follicular fluid stimulate hyperactivation of human spermatozoa after preincubation.

OBJECTIVE: To test the effects of steroid-containing media such as follicular fluid (FF) and serum and of steroid-free but human protein-rich medium on hyperactivation (HA) of human spermatozoa with and without a preincubation period. DESIGN: Analysis of HA using a computer-aided sperm analysis system. SETTING: Academic hospital and andrologic laboratory. PATIENTS: Twenty-six sperm samples were obtained from 26 different IVF patients. INTERVENTIONS: None. RESULTS: After a preincubation period of 3 hours, FF and serum enhanced the HA after 1 hour. A human plasma protein-rich solution did not. Without preincubation, no stimulation of HA was observed. CONCLUSION: Steroids may be involved in HA, and a preincubation period may be required for an appropriate FF-induced HA.

Study on the presence of homocysteine in ovarian follicular fluid.

OBJECTIVE: To study the presence of homocysteine, methionine and the vitamins folate, B12, and B6 in human ovarian follicular fluid (FF). DESIGN: Measurement of homocysteine, methionine, folate, and vitamins B12 and B6 in ovarian FF and blood. SETTING: Academic Department of Obstetrics and Gynecology at St. Radboud Hospital, Nijmegen, The Netherlands. PARTICIPANTS: Fourteen healthy women undergoing an IVF program. RESULTS: Detectable amounts of homocysteine and methionine were found in FF. Homocysteine concentrations were similar to those in serum. Methionine concentrations proved to be slightly but significantly lower than in corresponding serum samples. Concentrations of vitamins B12 and B6 were significantly lower in FF than in serum, whereas folate concentrations were not significantly different. A statistically significant correlation between corresponding serum and FF concentrations of homocysteine, folate, and vitamin B12 could be established. CONCLUSIONS: These data support the hypothesis that the ovum might be exposed to high homocysteine or low methionine concentrations, or both, and a lack of vitamins, which might be important in fertilization and early embryogenesis.

Antisperm antibodies and in vitro fertilization.

The purpose of this study was to investigate the influence of antisperm antibodies in the male, the female, or both partners on the outcome of in vitro fertilization treatment. The results in terms of ongoing pregnancies in the male and female antibody-positive group were the same as in the antibody-negative group. In the double antibody-positive group two of the three patients became pregnant. When high levels of antisperm antibodies were present on the spermatozoa, the fertilization rate was significantly reduced. In the female positive group no clear relationship between the antibody titer and the fertilization percentage could be detected. Abnormal semen quality was responsible for a much lower fertilization rate than the presence of antibodies. The conclusion of this study is that in vitro fertilization provides an equal change of conception in couples with antisperm antibodies in comparison with couples with no antibodies if the other semen parameters are normal.

Selective drop-out in successive in-vitro fertilization attempts: the pendulum danger.

Success rates from in-vitro fertilization (IVF) in the long term are dependent on selection procedures with regard to continuation into further IVF episodes. Publications on success rates in successive episodes will give incentives to adapt selection criteria, but if these publications do not deal explicitly with patient selection, the adaptations might change their direction every time: the pendulum danger.

Fetal heart rate in early pregnancy.

Heart rates were measured by transvaginal sonography twice weekly in ten first trimester fetuses in women who conceived after in-vitro fertilization (IVF) or zygote intra-fallopian transfer (ZIFT). From week 6 to week 9 of menstrual age a rapid increase of the mean heart rate was observed from 113 to 167 beats per min, followed by a slow decrease to 156 beats per min. A close correlation between crown-rump length and heart rate was established.

Is there influence of smoking on the mutagenicity of follicular fluid?

The mutagenicity of follicular fluid was examined in 24 patients, 12 smoking and 12 nonsmoking, who were treated in an in vitro fertilization program. The Salmonella microsome assay was used. It was found that the mutagenicity of follicular fluid was not influenced by the number of cigarettes smoked. Urine samples of smoking in vitro fertilization (IVF) patients however showed a dose-dependent elevation of the mutagenicity.