Biomedical subjects

I J Duijkers

Publications and source records attributed to I J Duijkers.

12 recordsLinked to original sources

PubMed2000

Ultrasonographic assessment of endocervix and cervical mucus in ovulatory menstrual cycles.

OBJECTIVE: In addition to the routinely used methods to evaluate the menstrual cycle, a new method will be described, assessing the aspect of the endocervix and the presence of cervical mucus by transvaginal ultrasonography. STUDY DESIGN: 36 healthy female volunteers with regular menstrual cycles participated in the study. Transvaginal ultrasonography was performed every other day until ovulation was observed, assessing the diameter of the largest ovarian follicle, endometrial thickness, the aspect of the endocervix, and the presence of cervical mucus. On the same days serum hormone concentrations were determined. RESULTS: Changes in the echodensity of the endocervix were observed in 35 volunteers, from 7 (1-19) (median and range) days before ovulation onwards. The presence of cervical mucus could clearly be observed in the preovulatory phase in 25 volunteers, from 3 (1-7) days before ovulation onwards. CONCLUSION: Preovulatory changes in the aspect of the endocervix and cervical mucus can be observed by transvaginal ultrasonography. Ultrasonography of the cervix may offer an additive diagnostic tool in fertility disorders and will, in many cases, make visual inspection of the cervix unnecessary.

Adolescent↗

PubMed1998

Single and multiple dose pharmacokinetics and pharmacodynamics of the gonadotrophin-releasing hormone antagonist Cetrorelix in healthy female volunteers.

The gonadotrophin-releasing hormone antagonist Cetrorelix is in advanced clinical development for the control of endogenous gonadotrophin secretion during the course of a fertility programme. The aim of the present study was to investigate the pharmacokinetics and pharmacodynamics of Cetrorelix following single and multiple s.c. administration of different doses. Thirty-six healthy female volunteers received either 0.25, 0.50 or 1.00 mg Cetrorelix, in a first menstrual cycle as single dose and in a second cycle as multiple dose (daily between cycle days 3 and 16). Frequent blood samples were collected for determination of Cetrorelix, follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and progesterone concentrations. Follicular growth was measured by transvaginal ultrasonography. After single administration of each dose, maximum Cetrorelix concentrations (Cmax) were reached after 1 h, and Cmax and area under curve (AUC) increased linearly with the dose. The median terminal half-life ranged from 5 to 10 h in the three different dose groups. FSH, LH, oestradiol and progesterone concentrations were suppressed, with a nadir at 6-12 h after Cetrorelix administration. During multiple administration, Cmax and AUC also showed dose-linearity. The median terminal half-life of Cetrorelix varied between 20 and 80 h. A dose-dependent suppression of FSH, LH and oestradiol concentrations was observed during treatment. After multiple administration, ovulation was delayed for 5, 10 and 13 days in the 0.25, 0.50 and 1.00 mg dose groups, respectively. In conclusion, Cetrorelix showed linear pharmacokinetics, and effectively delayed the LH surge.

Adolescent↗

PubMed1997

Pharmacodynamics and pharmacokinetics after repeated subcutaneous administration of three gonadotrophin preparations.

Recently, several new urinary gonadotrophin preparations have been developed, containing less luteinizing hormone (LH) activity than human menopausal gonadotrophin. Normegon is a gonadotrophin preparation with a follicle stimulating hormone (FSH)/LH ratio of 3:1; Follegon and Metrodin-HP are purified FSH preparations. The aim of the present randomized study was to compare pharmaco-dynamics, -kinetics and local tolerance of these preparations after repeated s.c. administration. Thirty-six healthy female subjects were treated with Lyndiol contraceptive pills for 5 weeks to suppress endogenous gonadotrophin concentrations. After 3 weeks of Lyndiol treatment, 150 IU of Normegon, Follegon or Metrodin HP were administered once daily, s.c. for 7 days. Blood samples were collected once daily during the fourth and fifth weeks of the study and assayed for FSH and oestradiol. After the last gonadotrophin injection, blood samples were collected more frequently to determine pharmacokinetic parameters of FSH. During the fourth and fifth study weeks, daily ultrasound measurements of follicular growth were performed. Endogenous FSH and LH values were extremely suppressed during Lyndiol treatment. Serum FSH values showed similar patterns in the three groups. The maximum FSH concentration was reached 9-11 h post-injection, the terminal half-life was 43-47 h. The preparations were bioequivalent with respect to FSH immunoreactivity. The number of follicles tended to be larger after Normegon than after Follegon and Metrodin HP treatment, though this was not statistically significant. Serum oestradiol concentrations were significantly higher after Normegon treatment. In general, s.c injections were well tolerated. In conclusion, the three preparations were bioequivalent with respect to FSH immunoreactivity. Nevertheless, the biological activity of Normegon tended to be higher than that of Follegon and Metrodin HP in Lyndiol-suppressed women.

Administration, Cutaneous↗

PubMed1995

Pharmacokinetics of two human menopausal gonadotrophin preparations after single intravenous administration during pituitary suppression.

A randomized study was performed in nine healthy women, to investigate pharmacokinetic parameters and bioequivalence of two human menopausal gonadotrophin preparations after i.v. administration. Endogenous gonadotrophin activity was suppressed by triptorelin administration. Humegon and Pergonal (225 IU of each) were injected i.v. in a cross-over way with an interval of 1 week. Blood samples were collected frequently and serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), specific LH, and human chorionic gonadotrophin (HCG) were determined by fluoroimmunoassays assays. Serum LH bioactivity was measured by an in-vitro bioassay. The area under curve (AUC) and half-life of FSH were respectively 431.5 IU h/l and 22.20 h for Humegon, and 402.6 IU h/l and 21.33 h for Pergonal. For both preparations, the (total) LH immunoactivity and in-vitro bioactivity of serum LH were very similar, and appeared to be a composite of specific LH and HCG activity. The AUC data of specific LH were 17.50 IU h/l for Humegon and 21.79 IU h/l for Pergonal respectively. The AUC and half-life of HCG were 153.7 IU h/l and 14.80 h for Humegon, and 134.1 IU h/l and 12.11 h for Pergonal. The two preparations were bioequivalent with respect to FSH and HCG immunoreactivity. Bioequivalence could not be proven for LH activity because of the small number of subjects.

Adolescent↗

PubMed1995

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.

Adult↗

PubMed1993

Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation.

The aim of the present study was to investigate whether reducing the amount of luteinizing hormone (LH) in gonadotrophic preparations impairs follicular growth in in-vitro fertilization (IVF) cycles during suppression of endogenous LH levels. A selected group of 20 IVF patients was randomly divided into two groups. One group was treated with Org 31338 [follicle stimulating hormone (FSH)/LH 3:1], the other group with Metrodin (purified FSH), both during pituitary down-regulation with buserelin. A fixed daily dose of 150 IU FSH i.m. was given. Serum concentrations of FSH, LH, oestradiol and progesterone were determined frequently and serial ultrasound examinations were performed. Multiple follicular growth with concomitant rise of oestradiol levels was observed in all cycles. The duration of the stimulation phase was shorter in the group treated with Org 31338 than in the group treated with Metrodin. The number of follicles and oocytes and the fertilization rate was larger and the mean embryo quality was higher in the Org 31338 group, but the differences did not reach statistical significance. No significant differences were found in hormonal values. In women with normal endocrine profiles, lowering of the LH activity in gonadotrophic preparations during gonadotrophin-releasing hormone agonist treatment results in adequate ovarian stimulation. However, a preparation with some LH needed a shorter stimulation than a purified FSH preparation. Whether the other beneficial effects of Org 31338 also occur in a larger population needs further investigation.

Adult↗

PubMedDate not supplied

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.

Adult↗

PubMedDate not supplied

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.

Adult↗

PubMedDate not supplied

Selective follicular reduction: what to do with the oocytes?

OBJECTIVE: To investigate the possible benefits of in vitro fertilization (IVF) of oocytes retrieved during selective follicular reduction of supernumerary follicles in non-IVF cycles. METHODS: Selective follicular reduction of supernumerary follicles was used to prevent ovarian hyperstimulation syndrome and multiple pregnancies in gonadotropin-stimulated cycles. We analyzed the data of 13 cycles (13 women) retrospectively. RESULTS: Three pregnancies occurred in these 13 cycles (23%), one after intra-uterine insemination and two after timed coitus. In all cycles, oocytes were retrieved, and in 10 cycles fertilization was achieved (77%); in 6 cycles cryo-preservation was successful (46%) and in 3 cycles embryo transfer (ET) was performed (23%). All embryos were of poor quality and no pregnancies occurred after ET of frozen-thawed embryos. The diagnostic value of fertilization failure seems to be low, since one of the patients who failed to show fertilization became spontaneously pregnant afterward. CONCLUSION: Based on our observations, the beneficial effect of IVF/cryopreservation during selective follicular reduction appears questionable.

Adult↗

PubMedDate not supplied

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.

Adult↗

PubMedDate not supplied

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.

Adult↗

PubMedDate not supplied

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.

Adult↗