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D de Ziegler

Publications and source records attributed to D de Ziegler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Vaginal progesterone in menopause: Crinone 4% in cyclical and constant combined regimens.

Compliance with hormone replacement therapy (HRT) is notoriously low despite ample documentation of clinical efficacy. The two major reasons given by women who discontinue HRT are uterine bleeding and side-effects. The recent development of a controlled and sustained vaginal progesterone gel allowed single daily application and made prolonged use such as for menopause possible. Here we report our clinical experience with two therapeutic options for HRT using natural progesterone administered vaginally. A first group of 69 menopausal women received the sustained release vaginal progesterone gel, Crinone 4% (45 mg daily) from days 1-10 of each calendar month with oestrogens taken continuously. A second group of 67 women received Crinone 4% twice weekly in conjunction with continuous oestrogen therapy. Endometrial thickness was evaluated before and after 6 months of treatment. Histological verification was obtained in all cases of abnormal bleeding. At 6 months, 63 out of 69 (91.9%) women receiving progesterone cyclically experienced predictable withdrawal bleeding. The vast majority, 54 (80.6%) of 67 women receiving Crinone in constant combined association with oestrogen therapy, remained amenorrhoeic throughout 6 months of therapy. All cases of abnormal bleeding were biopsied and no hyperplasia was seen. Our results indicate that both regimens using the sustained release vaginal progesterone gel controlled bleeding in HRT. Combined with the lower incidence of side-effects characteristic of vaginal progesterone, both vaginal progesterone regimens have the potential of improving HRT compliance.

Administration, Intravaginal↗
PubMed2000

Uterine contractility during the menstrual cycle.

The non-pregnant uterus shows different patterns of contractility during the menstrual cycle. A renewed interest in uterine contractility has resulted from reports of non-invasive ultrasound (US) based studies. To clarify the changes in uterine contractility occurring throughout the menstrual cycle, we prospectively studied uterine contractions (UC) at six representative stages with US and intrauterine pressure (IUP) based approaches in 30 cycling volunteers. Results showed UC frequency could be measured by either US or IUP. UC amplitude and resting pressure tone could only be assessed by IUP. Conversely, direction of UC displacement could only be assessed by US. UC frequency increased at mid-cycle and decreased throughout the luteal phase suggesting oestradiol and progesterone exert positive and negative actions on uterine contractility, respectively. UC amplitude increased throughout the menstrual cycle to maximum values in the late luteal phase. Retrograde UC were most frequent at mid-cycle and convergent ('opposing') UC predominated during the luteal phase. While the former pattern ensures sperm transport, the latter may facilitate embryo implantation. In conclusion, UC changes throughout the menstrual cycle assessed by US and IUP emphasize the hormonal dependence of uterine contractility. Although UC patterns favouring sperm transport appear regulated by oestradiol, uterine quiescence and the dominance of convergent UC prevailing at the time of implantation are linked to progesterone. These data will serve to identify and treat possible dyskinetic changes in uterine contractility, particularly in women suffering from infertility, endometriosis, and dysmenorrhea.

Adult↗
PubMed2000

Hormonal influence on the uterine contractility during ovarian stimulation.

High-frequency uterine contractions (UC) at the time of embryo transfer have been shown to hamper the outcome of in-vitro fertilization (IVF). As UC are postulated to be hormone-regulated, we aimed to investigate the role of plasma oestradiol and progesterone concentrations on UC during ovarian stimulation for IVF. A total of 59 women were studied on the day of administration of human chorionic gonadotrophin (HCG) and embryo transfer. Plasma oestradiol and progesterone concentrations were measured, and 5 min ultrasound scans of the uterus were digitized with an image analysis system to assess UC frequency and direction. Cycles were sorted according to whether progesterone concentrations on the day of embryo transfer were < or =100 (n = 34) or >100 (n = 25) ng/ml. On the day of HCG, UC frequency was similar in both groups at 4.5+/-0.2 and 4.6+/-0.3 UC/min (mean +/- SE) respectively. On the day of embryo transfer, UC frequency remained steady in the low progesterone group, whereas it decreased (3.5+/-0.2 UC/min) in the high progesterone group (P < 0.001), and was negatively correlated with progesterone concentrations (r = -0.56; P < 0.001). No influence of oestradiol on UC was noticed. These observations confirm the utero-relaxing effects of progesterone in the non-pregnant uterus and support the administration of progesterone before embryo transfer to increase tissue concentrations and improve the outcome of IVF.

Adult↗
PubMed1999

Computerized assessment of endometrial echogenicity: clues to the endometrial effects of premature progesterone elevation.

OBJECTIVE: To determine whether premature progesterone elevation affects the timing of hyperechogenic transformation of the endometrium during the early luteal phase of controlled ovarian hyperstimulation (COH) cycles. DESIGN: Prospective analysis. SETTING: Assisted Reproduction Unit, Hôpital Antoine Béclère, Clamart, France. PATIENT(S): Fifty-nine women undergoing 59 IVF-ET cycles. INTERVENTION(S): Patients underwent COH with a GnRH agonist and hMG. Endometrial echogenicity was assessed on the days of hCG administration, oocyte retrieval, and ET. Results are expressed as the extent of submyometrial hyperechogenic area in relation to the total endometrial surface as determined by a computer-assisted analysis system. Patients were sorted according to whether their plasma progesterone level exceeded 0.9 ng/mL (n = 26) or not (n = 33) on the day of hCG administration. MAIN OUTCOME MEASURE(S): Endometrial echogenicity. RESULT(S): On the day of hCG administration, the degree of endometrial echogenicity was similar in both groups (41% vs. 40%), but after hCG administration, it increased significantly faster in the high progesterone group than in the low progesterone group (70% vs. 63% at oocyte retrieval and 90% vs. 79% at ET, respectively). CONCLUSION(S): End-follicular phase elevation in plasma progesterone (>0.9 ng/mL on the day of hCG administration) was associated with a faster increase in endometrial echogenicity during the early luteal phase of COH cycles. This observation is consistent with the hypothesis that premature progesterone elevation hastens the secretory transformation of the endometrium.

Adult↗
PubMed1999

Programming ovulation in the menstrual cycle by a simple innovative approach: back to the future of assisted reproduction.

OBJECTIVE: To synchronize the intercycle FSH elevation with exogenous E2 for programming ovulation in the menstrual cycle. DESIGN: Open single-arm study. SETTING: Teaching hospital. PATIENT(S): Twenty-six patients with infertility whose menstrual cycles normally lasted 25-35 days and who underwent our routine programming method for postcoital tests and ovulation evaluations. INTERVENTION(S): Participants received estradiol valerate (2 mg) twice a day from day 25 of the previous cycle until 1-15 days after the onset of menses. Women had ultrasonography on the last day of E2 treatment or on functional day 0 and 13 days later or on functional day 13. Hormones were determined on functional days 0, 3, 9, and 13. The increase in FSH in response to E2 withdrawal was defined as deltaFSH. MAIN OUTCOME MEASURE(S): LH surge and other ovulatory indices on functional day 13. RESULT(S): On functional day 13, 73% of the women had an LH surge. Fifteen percent had evidence of previous ovulation with low LH and elevated plasma P levels, and the remaining 12% had low LH levels and no evidence of past or imminent ovulation. Women with evidence of early ovulation were older and had higher FSH signal amplitude. CONCLUSION(S): It is feasible and practical to program ovulation in the menstrual cycle with exogenous E2. In 73% of women, the true duration of the follicular phase (intercycle FSH elevation to LH surge interval) remained constant (13 days). Hence, common fluctuations in menstrual cycle length mainly result from variations in the timing of the intercycle FSH elevation. Although rare, truly short follicular phases also exist (15%). This simple and practical system for programming natural ovulation offers new possibilities for using the menstrual cycle in assisted reproductive technology, at least in selected individuals.

Adult↗
PubMed1998

The hormonal control of endometrial receptivity: estrogen (E2) and progesterone.

While the number of identified substances produced by the ovary increases steadily, it remains remarkable that the sole use of exogenous estrogen (E2) and progesterone (P) can prime optimal endometrial receptivity in women whose ovaries have failed or are absent. Early work showed that a marked leeway existed in the acceptable duration of the E2-only phase of endometrial priming. Subsequently, a sequence of transformations are induced by exogenous progesterone that reproduces classical findings made in the menstrual cycle. Secretory changes in endometrial glands are best seen between the 4th and 6th day of progesterone administration (day 18-20 of an ideal cycle where progesterone exposure starts on day 15). Predecidual changes of the endometrial stroma are apparent starting on the 10th day of progesterone exposure (day 24). Contrary to earlier belief, even maximal alterations in the plasma E2 to progesterone ratio fails to alter the endometrial morphology of either glands or stroma. More recently it has been recognized that E2 and progesterone also affect uterine contractility. It has been postulated that excessively high levels of E2 may increase uterine contractility and adversely affect implantation rates in in-vitro fertilization (IVF). Exogenous progesterone has been shown to exert utero-relaxing effects and it has been hypothesised that progesterone supplementation before embryo transfer (ET) may improve receptivity in IVF.

Androgens↗
PubMed1998

Synchronization of endogenous and exogenous FSH stimuli in controlled ovarian hyperstimulation (COH).

We have previously observed that exogenous oestradiol can delay the intercycle increase in plasma follicle stimulating hormone (FSH). The increase in plasma FSH that follows discontinuation of exogenous oestradiol peaks after 3 days. We have now studied the possibility of using exogenous oestradiol to synchronize the increase in endogenous FSH with the onset of human menopausal gonadotrophin (HMG) treatment in controlled ovarian hyperstimulation (COH). A total of 30 women aged 35.1+/-6.3 years (mean+/-SD) undergoing ovarian stimulation received 2 mg of oestradiol valerate twice daily starting on day 25 of the previous menstrual cycle until the first Tuesday following menses. Ovarian stimulation was initiated 3 days later. On the last day of oestradiol treatment, plasma oestradiol, FSH and luteinizing hormone (LH) (mean+/-SEM) were 566+/-53 (pmol/l), 3.8+/-0.4 (IU/l) and 5.5+/-0.8 (IU/l) respectively. After 3 days, the FSH and LH (mean+/-SEM) had increased to 6.7+/-0.7 and 6.9+/-0.7 (IU/l) respectively while oestradiol decreased to 251+/-29 (pmol/l). The mean number (+/-SEM) of HMG ampoules used was 25.1+/-2.7 and treatment lasted 11.3+/-0.9 days. Five women became pregnant for a pregnancy rate (ongoing) of 19 (15)%. If all women aged >40 years (six women who did not become pregnant) were excluded from analysis the pregnancy rate (ongoing) was 24 (19%). These results indicate that exogenous oestradiol can safely be used for the synchronization of endogenous and exogenous FSH stimuli in COH. This approach provides the practical advantage of permitting an advanced timing of the onset of COH treatments when gonadotrophin-releasing hormone (GnRH) agonists are not used, which improves treatment convenience for patients and team members alike. Further development of this model may enable control of the onset of natural cycles which may find practical applications for timing assisted reproductive techniques (intrauterine insemination or in-vitro fertilization) in the natural cycle.

Adult↗
PubMed1998

Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization.

To investigate the possible consequences of uterine contractions (UC) as visualized by ultrasound (US) on in-vitro fertilization (IVF)-embryo transfer outcome, we studied prospectively 209 infertile women undergoing 220 cycles of controlled ovarian stimulation. Inclusion criteria were age < or = 38 years, a morphologically normal uterus, and at least three good quality embryos transferred. Just before embryo transfer, women underwent 5 min digital recordings of the uterus using US image analysis software for UC assessment. Plasma progesterone and oestradiol concentrations were measured. Four groups were defined according to UC frequency: < or = 3.0 (n = 53), 3.1-4.0 (n = 50), 4.1-5.0 (n = 43), and > 5.0 (n = 74) UC/min respectively. Patients, controlled ovarian hyperstimulation and embryology characteristics were comparable in all groups. A stepwise decrease in clinical and ongoing pregnancy rates as well as in implantation rates occurred from the lowest to the highest UC frequency groups (53, 36, 21; 46, 32, 20; 23, 19, 10; and 14, 11, 4%; P < 0.001). Plasma progesterone and UC frequency were negatively correlated (r = -0.34, P < 0.001). Direction of UC did not affect embryo transfer outcome. As this study was controlled strictly for confounding variables and UC were assessed objectively by a computerized system, its results indicate that high frequency UC on the day of embryo transfer hinder IVF-embryo transfer outcome, possibly by expelling embryos out of the uterine cavity. The negative correlation between UC frequency and progesterone concentrations supports the uterine relaxing properties of progesterone.

Chorionic Gonadotropin↗
PubMed1997

[Cardiovascular physiopathology of ovarian hormones].

Epidemiological data indicate that women are less likely to suffer from coronary heart disease (CHD) than men of the same age. This difference vanishes however after menopause suggesting that it is the hormones produced by the ovaries that are responsible for the relative cardioprotection that women enjoy before menopause. In spite of the favorable impact of oral estrogen treatments on the lipid profile it is believed today that estrogens act mainly through direct effects on vessels. Estrogens have vasodilative properties, exert anti proliferative effects on the endothelium and alter the response of vessels to various stimuli (vaso-reactivity) such as Acetylcholine (Ach). Direct assessment of large vessel wall thickness or Intima Media Thickness (IMT) is considered as the most predictive parameter of cardiovascular risk today and may serve to single out women who must receive HRT for cardiovascular reasons.

Adolescent↗
PubMed1997

Consequences of premature progesterone elevation on the outcome of in vitro fertilization: insights into a controversy.

OBJECTIVE: To investigate whether the consequences of premature P elevation on IVF-ET outcome are modulated by the quality of the ovarian response to controlled ovarian hyperstimulation (COH). DESIGN: Retrospective analysis. SETTING: Assisted Reproduction Unit, Clamart, France. PATIENT(S): One thousand twelve women undergoing 1,189 IVF-ET cycles. INTERVENTION(S): Patients underwent COH with a time-released GnRH agonist and hMG. The ovarian response to COH was classified as strong (< or = 50 hMG ampules, peak E2 levels > 2,500 pg/mL, and > or = 10 mature oocytes; n = 340), weak (> 50 hMG ampules, peak E2 levels < or = 1,500 pg/mL, and < or = 5 mature oocytes; n = 285), or intermediate (remaining cases; n = 564). The IVF-ET outcome in each group was analyzed according to whether or not plasma P levels exceeded 0.9 ng/mL. MAIN OUTCOME MEASURE(S): Pregnancy rates (PRs). RESULT(S): Clinical PRs were similar irrespective of low or high P levels in the strong (30% and 34%, respectively) and intermediate (31% and 30%, respectively) groups. However, in the weak group, P levels > 0.9 ng/mL were associated with lower PRs (3.2% and 23%, respectively). CONCLUSION(S): In the presence of an adequate response to COH, P levels > 0.9 ng/mL were not associated with lower PRs, indicating that good embryo quality may compensate for the adverse endometrial effects of P. Conversely, when the response to COH was weak, premature P elevation led to drastically reduced PRs.

Adult↗
PubMed1997

Premature plasma progesterone and androgen elevation are not prevented by adrenal suppression in in vitro fertilization.

OBJECTIVE: To investigate the effects of adrenal suppression with dexamethasone (DEX) on P and androgen profiles during controlled ovarian hyperstimulation (COH) for IVF-ET. DESIGN: Prospective controlled trial. SETTING: In vitro fertilization program, Clamart, France. PATIENT(S): One hundred twenty IVF-ET candidates aged 25 to 39 years undergoing 120 COH cycles. INTERVENTION(S): Group A: 60 women received a time-release GnRH agonist (GnRH-a) on cycle day 2. After pituitary desensitization was confirmed, 1 mg/d DEX was administered daily until hCG. Ovarian stimulation with hMG was started on the 7th day of DEX. Group B: 60 other women received an identical treatment except DEX was omitted. MAIN OUTCOME MEASURE(S): Plasma E2, P, androstenedione (A), and T were measured 18 days after GnRH-a, on the 7th day of DEX in group A, and on the day of hCG. RESULT(S): Peak plasma E2 levels were similar in groups A and B. After GnRH-a, P and androgen levels were low in both groups. In group A, an additional decrease in these hormones was observed after 7 days of DEX. During COH, we observed similar absolute increases of P, A, and T in groups A (+0.52, +1.56, and +0.12 ng/mL, respectively) and B (+0.55, +1.66, and +0.17 ng/mL, respectively). CONCLUSION(S): As expected, DEX lowered additionally P, A, and T levels from values achieved after GnRH-a alone, reflecting the adrenal contribution to the circulating levels of these hormones at baseline. Yet, the net increases in P, A, and T seen in COH were unaltered by DEX treatment, indicating that this phenomenon results solely from an effect of exogenous gonadotropins on the ovary.

Adrenal Glands↗
PubMed1997

Targeted drug delivery in gynaecology: the first uterine pass effect.

The objective was to verify the hypothesis of a 'first uterine pass effect' or direct preferential vagina-to-uterus transport, suggested by the evidence of higher than expected uterine tissue concentrations after vaginal administration of progesterone; we used a human ex-vivo uterine perfusion model. A mixture of tritiated (3H) and unlabelled progesterone was applied to the cuff of vaginal tissue remaining attached to the cervix after hysterectomy. At the end of the perfusion period (up to 12 h), 3H and 14C radioactivity was measured in samples of uterine tissue. Tritiated water and [14C]dextran were tested to determine the extent of non-specific vagina-to-uterus transport (leaks). Finally, sections of uterine tissue exposed only to [3H]progesterone were prepared for autoradiography. By 4-5 h after application progesterone had diffused to the entire uterus and had reached a steady state; 4 h after application, progesterone concentrations reached 185 +/- 155 and 254 +/- 305 ng/100 mg of endometrial and myometrial tissue respectively. Endometrial extraction of progesterone was higher when the experiment was performed on uteri obtained during the luteal phase (280 +/- 156 ng/100 mg of endometrial tissue) than those removed during the proliferative phase of the menstrual cycle (74 +/- 28 ng/100 mg of endometrial tissue). These data demonstrate that a 'first uterine pass effect' occurs when drugs are delivered vaginally, thereby providing an explanation for the unexpectedly high uterine concentrations relative to the low serum concentration observed after vaginal administration. Hence, the vaginal route permits targeted drug delivery to the uterus, thereby maximizing the desired effects while minimizing the potential for adverse systemic effects.

Administration, Intravaginal↗
PubMed1996

Premature progesterone elevation does not alter oocyte quality in in vitro fertilization.

OBJECTIVE: To clarify whether premature P elevation during controlled ovarian hyperstimulation (COH) for IVF-ET affects adversely oocyte-embryo quality. DESIGN: Controlled clinical study. PATIENTS: We studied 102 fertile donors undergoing 106 oocyte retrievals and 117 recipients undergoing 162 ET. INTERVENTIONS: Donors underwent COH with a time-release GnRH agonist and hMG. All recipients had inactive or absent ovaries and were primed with E2 and P. MAIN OUTCOME MEASURES: Measurement of LH, P and E2; characteristics of COH; cleavage, pregnancy, and implantation rates. RESULTS: According to donors' plasma P levels on the day of hCG, two groups were defined: P < or = 0.9 ng/mL (conversion factor to SI unit, 3.18), group A, and P > 0.9 ng/mL, group B. Similar results of cleavage (65% and 72%), clinical (30% and 29%), and ongoing pregnancy (20% and 18%), and implantation (14% and 15%) rates were observed in both groups, respectively. CONCLUSIONS: The lack of difference in cleavage, pregnancy, and implantation rates between both groups suggests that preovulation increase in P production does not alter oocyte-embryo quality. Hence, the reported adverse effects on IVF outcome of pre-hCG elevation of P is likely to reflect an impaired endometrial receptivity in the high P group.

Adult↗
PubMed1995

[Non-oral administration of progesterone: experiences and possibilities of the transvaginal route].

Recent development of transdermal therapy permits application of estrogen, usually produced in the ovaries, in physiological dosage by means of continuous release from either an epidermal patch or dermal application of a gel. Transdermal therapy with progesterone, however is impossible due to poor dermal absorption and high dose requirements (release from corpora lutea: 25 mg/24 hours). Two other possibilities have been proposed. On one hand it is possible to apply norethisterone-acetate (NETA), another gestagen, epicutaneously. This mode of administration carries the same problems as oral application thus allowing for a dose reduction. On the other hand progesterone can be applied vaginally. This mode leads to significantly higher plasmatic concentrations of progesterone and has effects on the uterine mucosa similar to those in a normal cycle. This modality thus permits application of estradiol and progesterone in a physiological manner by a non oral route. It appears particularly interesting in patients at cardiovascular risk.

Administration, Intravaginal↗
PubMed1995

Endometrium preparation with exogenous estradiol and progesterone for the transfer of cryopreserved blastocysts.

OBJECTIVE: To determine the implantation rates of cryopreserved blastocysts using controlled E2 and P replacement cycles in women with functioning ovaries. DESIGN: Retrospective clinical study. SETTING: University teaching hospital. PATIENTS: Infertile women with cryopreserved blastocysts obtained from previous IVF attempts. INTERVENTIONS: Exogenous E2 was administered orally from cycle day 1 and P was started transvaginally from day 15. Blastocysts were transferred on the 5th day of endometrial exposure to P (day 19). MAIN OUTCOME MEASURES: Blastocyst implantation rate and pregnancy rate (PR). RESULTS: Ninety-eight percent of blastocysts survived thawing: 67 were transferred in 42 women. Eight pregnancies occurred giving a PR of 19% per ET and 11.9% per blastocyst. CONCLUSION: The high PR observed after transferring blastocysts on the 5th day of endometrial exposure to P in controlled E2 and P replacement cycles speaks for a forward slide of the window of transfer in case of blastocysts.

Adult↗
PubMed1995

Physiopathology of premature progesterone elevation.

OBJECTIVE: To determine the effects of the last hMG administration on plasma P and androgen profiles during controlled ovarian hyperstimulation (COH) for IVF-ET. DESIGN: Controlled clinical study. SETTING: The IVF-ET program of a tertiary outpatient care center, Hôpital A. Béclère, Clamart, France. PATIENTS: Nine IVF-ET candidates aged 25 to 36 years having presented normal responses to COH in previous IVF-ET cycles. INTERVENTIONS: Controlled ovarian hyperstimulation was induced for IVF-ET using hMG after endogenous gonadotropins were suppressed with a time-release GnRH agonist. Just before the last hMG administration (225 IU), the participants were hospitalized for 24 hours for serial blood sampling. These occurred before (baseline) and after hMG administration, every 30 minutes for 1 hour, hourly for 4 hours, and every 3 hours for the remaining part of a 24-hour post-hMG observation period. MAIN OUTCOME MEASURE: Measurement of P, T, androstenedione (A), E2, FSH, and LH. RESULTS: Plasma P and androgens (T and A) increased significantly, reaching peak values 12 to 15 hours after hMG administration and decreased progressively thereafter, to reach values not significantly different from baseline 24 hours after hMG administration. Plasma E2 levels increased progressively and steadily during the 24-hour observation period. Plasma FSH levels remained constant after hMG administration while LH stayed undetectable. CONCLUSION: In COH cycles induced for IVF-ET, the hormonal profile after the last hMG injection suggests that hMG triggers an increase in plasma P and androgens that culminates 12 to 15 hours after hMG administration. This elevation in plasma P and androgens observed after hMG administration is likely to reflect a direct action of the LH and/or FSH components of hMG on granulosa cells. In some women these hormonal consequences of hMG treatment may impair endometrial receptivity in IVF-ET cycles.

Adult↗