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Biomedical subjects

D D Braat

Publications and source records attributed to D D Braat.

48 records · Page 3Linked to original sources

Serum and follicular fluid levels of insulin-like growth factor I (IGF-I), IGF-II, and IGF-binding protein-1 and -3 during the normal menstrual cycle.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have important regulatory functions in ovarian follicular development. Although most studies have investigated the IGF system in ovarian cells in vitro, investigation of the IGF system in the peripheral circulation and in follicles of varying sizes throughout the menstrual cycle in large numbers of subjects has been lacking. In the current study we performed daily IGF-I, IGF-II, IGFBP-1, and IGFBP-3 measurements in 9 healthy regularly cycling volunteers throughout the menstrual cycle. In addition, we investigated IGF-I, IGF-II, IGFBP-1, and IGFBP-3 levels in 13 samples of androgen-dominant follicular fluid [FFa androstenedione to estradiol (AD:E2) ratio, > 4] and 19 samples of estrogen-dominant follicular fluid (FFe; AD:E2 ratio, 4) obtained from 21 regularly cycling subjects and in 18 samples of fluid from luteinizing follicles obtained from patients undergoing in vitro fertilization (IVF) treatment (FFivf). IGF-I, IGF-II, IGFBP-1, and IGFBP-3 were measured using two-site immunoradiometric assays. No significant day to day differences were observed in IGF-I, IGF-II, IGFBP-1, and IGFBP-3 levels across the menstrual cycle. Median IGF-II levels in FFe (630 ng/mL; range, 212-1000) were significantly higher compared to those in FFa (474 ng/mL; range, 272-603; P = 0.002). Median IGFBP-3 levels in FFe (2955 ng/mL; range, 388-3448) were also significantly higher than those in FFa (2352 ng/mL; range, 756-2604; P = 0.003). Median IGF-I (192 ng/mL; range, 29-256) and IGFBP-1 (12 ng/mL; range, 2-281) levels in FFe were not significantly different from those in FFa [149 (range, 22-232) and 21 (range, 5-32) ng/mL, respectively). In contrast, significantly lower IGFBP-1 levels were found in FFe compared to FFivf (79 ng/mL; range, 57-234; P = 0.002), whereas there was no significant difference between FFe and FFivfe IGF-I, IGF-II, or IGFBP-3 levels, respectively. IGF-II levels were correlated with follicle diameter (r = 0.52; P = 0.002), cycle day (r = 0.47; P = 0.0065), E2 levels (r = 0.53; P = 0.003), AD:E2 ratio (r = -0.58; P = 0.001), and P concentrations (r = 0.60; P = 0.001) in all follicles, whereas no such correlations were found with IGF-I. In conclusion, as circulating levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-3 are not menstrual cycle dependent, it is unlikely that these growth factors and these binding proteins play an endocrine role in cyclic ovarian follicle development, although both cycle-dependent delivery to the ovary and modification of their actions locally within the ovary cannot be excluded. With regard to FF1 the findings that IGF-II levels in FF1 are elevated compared to those in FFa and correlate with follicular functional status support a role for IGF-II during development of the dominant follicle. In addition, as IGFBP-3 in estrogen-dominant follicles mirrors the rise of IGF-II, this IGFBP may be a primary regulator of IGF-II action within the estrogen-dominant follicle. Finally, the finding of elevated levels of IGFBP-1 in luteinizing (IVF) follicles suggests an important role for this peptide in corpus luteum regulation.

Adult↗

Cumulative conception and live birth rates after the treatment of anovulatory infertility: safety and efficacy of ovulation induction in 200 patients.

An analysis was performed on the cumulative conception rates, cumulative live birth rates and adverse effects of ovulation induction in patients with anovulatory infertility attending a single unit over an 11-year period. A total of 200 patients were included, 103 with clomiphene-resistant polycystic ovary syndrome (PCOS), 77 with hypogonadotrophic hypogonadism (HH) and 20 with weight-related amenorrhoea (WRA). Ovulation induction was performed using a number of protocols in which pulsatile luteinizing hormone-releasing hormone was administered s.c. or i.v. and gonadotrophins (human menopausal gonadotrophins or follicle-stimulating hormone) were administered i.m. The cumulative conception and live birth rates in the first course of therapy and after 12 cycles of treatment were, respectively, 73.2 and 62.4% in PCOS patients, 82.1 and 65.4% in the HH group and 95.0 and 85.3% in the WRA group. The miscarriage rates for all courses of treatment were 15.5% in PCOS patients, 22.9% in HH patients and 32.3% in WRA patients which resulted in cumulative live birth rates that were not significantly different. The median number of cycles and ovulations to achieve a pregnancy was 2 in all groups. The multiple pregnancy rate was significantly greater in women with PCOS (17.9%) than in women with HH (3.6%, P = 0.0052, 95% CI 5.12-23.36%) but not WRA (3.2%, P = 0.07, 95% CI 4.35-24.92%). The rate of multiple pregnancy fell after the introduction of monitoring by transvaginal ultrasound. Correction of anovulatory infertility by appropriately selected ovulation induction regimens results in cumulative conception and live birth rates indistinguishable from normal.

Amenorrhea↗

Multiple follicular growth under pulsatile gonadotrophin releasing hormone stimulation.

Pulsatile gonadotrophin releasing hormone (GnRH) treatment in patients with secondary hypothalamic amenorrhoea results in higher multiple pregnancy rates than expected. This multiple pregnancy rate is significantly higher when conception occurs during the first treatment cycle and when higher pulse doses are used. This is probably due to higher follicle stimulating hormone (FSH) levels, leading to multiple follicular growth. The endocrinology of pulsatile i.v. GnRH treatment cycles in patients with hypothalamic amenorrhoea as well as in patients with normal cycles revealed higher FSH levels during the first days of treatment compared with unstimulated control cycles. It was possible to induce multiple follicular growth in normally cycling women with pulsatile GnRH. To prevent multiple pregnancies in patients with hypothalamic amenorrhoea, a low pulse dose should be used, especially during the first treatment cycles.

Amenorrhea↗

Induction of multiple follicular growth by pulsatile gonadotrophin-releasing hormone (GnRH) treatment in women with normal cycles: the role of the route of administration.

In a prospective study, seven patients with normal menstrual cycles were treated with pulsatile gonadotrophin-releasing hormone. They received one cycle of intravenous (i.v.) therapy and one cycle of subcutaneous (s.c.) therapy. Another four volunteers with normal cycles were treated for one s.c. cycle only. Cycles were compared to each other and to the normal unstimulated cycles of 14 other volunteers. Multiple follicular development could be achieved using both the i.v. and the s.c. routes. However, the i.v. route showed significantly higher luteinizing hormone (LH) and luteal steroid levels. Comparing s.c. cycles to controls, significantly lower LH levels were observed, resulting in significantly lower steroid production if calculated per large follicle. We conclude that the i.v. route is superior to the s.c. route in inducing multiple follicular growth in women with normal cycles.

Adult↗

Life table analysis of fecundity in intravenously gonadotropin-releasing hormone-treated patients with normogonadotropic and hypogonadotropic amenorrhea.

The success of pulsatile intravenous (IV) gonadotropin-releasing hormone (GnRH) treatment in patients with normogonadotropic and hypogonadotropic amenorrhea was studied retrospectively using life table analysis. Two hundred forty-four ovulatory cycles in 48 normogonadotropic and hypogonadotropic patients were evaluated. The cumulative conception rate after 12 cycles was 93%, with a mean conception rate of 22.5% per cycle. Comparing cycles 1 to 6 with cycles 7 to 12, no significant difference in conception rate was observed. Subdivisions were made relative to the presence of additional infertility factors, history of weight loss, actual weight, estrogenic status, and primary versus secondary amenorrhea. The life table curves of patients either with or without other infertility factors were significantly different. No statistically significant differences were found in the other subdivisions. It is concluded that IV GnRH therapy is highly successful in patients with normogonadotropic and hypogonadotropic amenorrhea, especially if no other infertility factors are present.

Adult↗

Endocrinology of gonadotropin-releasing hormone induced cycles in hypothalamic amenorrhea: the role of the pulse dose.

OBJECTIVE: To find the treatment regimen giving a maximum chance of ovulation and a minimal chance of multiple follicular development in pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with hypothalamic amenorrhea. DESIGN: We propectively studied the endocrinology of cycles induced with 5, 10, and 20 micrograms GnRH pulse doses, randomly assigned per patient, comparing this with the endocrinology of spontaneous menstrual cycles. SETTING: All patients were treated at the Academic Hospital of the Vrije Universiteit, Division of Reproductive Endocrinology and Fertility. PATIENTS: Fifteen patients with hypothalamic amenorrhea were treated for one to three cycles; 14 normally cycling volunteers were studied for one cycle. MAIN OUTCOME MEASURE: Number of ovulations per pulse dose; luteinizing hormone, follicle-stimulating hormone, total urinary estrogens (Es), and pregnanediol were measured per cycle day and per stimulation day. RESULTS: The endocrinology of all ovulatory cycles remained within the normal range. First treatment cycles showed significantly higher ovulation rates compared with subsequent cycles. Significantly more anovulation was observed in cycles with 5-micrograms pulse doses. Luteal Es were significantly higher in induction cycles compared with controls. CONCLUSIONS: The optimum treatment regimen should be to start induction with 5 micrograms/pulse in the first cycle and to raise the dose to 10 micrograms/pulse in subsequent cycles, regardless of the outcome of the first cycle. After ovulation, the pulse interval should be changed to 240 minutes.

Adult↗

Multiple follicular development in women with normal menstrual cycles treated with pulsatile gonadotrophin-releasing hormone.

In a prospective study, 15 patients with normal menstrual cycles were treated with pulsatile gonadotrophin-releasing hormone (GnRH) for one to four cycles. These cycles were compared to unstimulated cycles of 14 volunteers. There was a surprisingly stable number of large (greater than or equal to 14 mm diameter) follicles per patient. The number of large follicles in induction cycles was significantly greater than in controls (2.4 versus 1.07). This was due to significantly higher follicle stimulating hormone levels during the first days of treatment. Our data provide a rationale for the use of pulsatile GnRH for a safe and mild form of stimulation in assisted reproductive therapies.

Adult↗

Pregnancy outcome in luteinizing hormone-releasing hormone induced cycles: a multicentre study.

In a retrospective international study 223 pregnancies induced with pulsatile hormone-releasing hormone (LH-RH) were evaluated. In patients with hypothalamic amenorrhea (HA) and polycystic ovarian disease (PCOD) the abortion rate was similar (10% vs 8.7%). The premature delivery rate was significantly higher, however, in the patients with HA, but this could be explained by the higher incidence of multiple pregnancies in this group. Thirty multiple pregnancies were observed in the HA group (n = 174) compared with none in the PCOD group (n = 24; p less than 0.05). The incidence of multiple pregnancies in the HA group correlated to the pulse dose (p less than 0.05). The 1st treatment cycle resulted in more multiple pregnancies than did subsequent cycles (p less than 0.05). Difference in pulse interval did not affect the incidence of multiple pregnancies, nor did the route of administration (intravenous or subcutaneous). The incidence of congenital anomalies was comparable to that with spontaneously achieved pregnancies.

Adult↗

Twin pregnancy: case reports illustrating variations in transfusion syndrome.

The twin transfusion syndrome is diagnosed in 5.5% to 14.6% of monochorionic twins and the classical picture reveals a small anemic donor and a large plethoric recipient. Many other clinical discrepancies have been described. Today, by ultrasound it is possible to diagnose the syndrome in (early) pregnancy. In these case reports different clinical pictures and the importance of ultrasound are described. In twin pregnancies repeated ultrasound examinations should be considered with the consequences of vascular anastomoses.

Adult↗

A neuropeptide in human semen: oxytocin.

The neuropeptide oxytocin (OT) has been detected in testis and epididymis of several mammals. The peptide affects steroidogenesis and sperm transport in vivo. Effects of OT on sperm motility in vitro seems to be contradictory. As no data are available on the presence of OT in human semen and on the relationship of OT with sperm characteristics, we assessed OT level in semen samples in 3 groups of patients: (I) normozoospermic, (II) astheno-/oligo-/teratozoospermic, and (III) azoospermic subjects. Furthermore, we studied the relationship between the concentration of OT in semen and the sperm characteristics. OT was measured in seminal plasma by radioimmunoassay after extraction. OT semen levels did not differ in control patients (I: 1.72 +/- 0.78 pg/mL; n = 10), patients with poor semen quality (II: 1.66 +/- 0.91 pg/mL; n = 11), or in vasectomized patients (III: 1.28 +/- 0.65 pg/mL; n = 11). No statistically significant relationships between the OT levels and sperm characteristics (density: 0.0693; total sperm count: 0.0845; percentage of motility: 0.1341; morphology: 0.3478) have been found. The neurosecretory peptide oxytocin is present in human seminal plasma of normal as well as of vasectomized subjects. OT is not only derived from the testis; OT levels in poor semen samples are not different from controls. No relationship was found between OT seminal plasma levels and sperm characteristics.

Humans↗