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Biomedical subjects

D de Ziegler

Publications and source records attributed to D de Ziegler.

At least 19 recordsLinked to original sources

[Early pregnancy termination: what the generalist should know].

Termination of pregnancy before 12 weeks after the last menstrual period is requested by an important number of women. We review the legal framework of abortion in Switzerland and the most used methods for medical abortion precising their contra-indications and most frequent complications. Very rare but fatal cases of infection following medical abortion (with mifepristone and misoprostol) were recently described. We present their clinical characteristics and discuss the related physiopathological process.

Abortion, Legal↗

[Identification of the intercycle FSH signal in urine samples (uFSH)].

OBJECTIVE: The intercycle FSH signal that initiates follicular recruitment and marks the functional onset of the menstrual cycle is of small amplitude and while it commonly occurs on cycle day 3, this often varies. Hence, its identification and measurement in serum (sFSH) requires serial daily samplings. We attempted to determine whether urine measurements of FSH (uFSH) could offer a non-invasive alternative, using a model where the intercycle FSH signal is controlled by timely use of exogenous E2. PATIENTS AND METHODS: Pilot prospective trial in 21 infertile women having received E2, from day 25 of the previous cycle until the 1st Friday after menses. Blood and first void urine samples were collected, starting on the last day of E2 (baseline) for assessing FSH and creatinin. A sonogram was performed for identification of maturing follicles (>12 mm). RESULTS: uFSH and uFSH/Cr showed good correlation with sFSH (R = 0.52 and 0.63, P < 0.0001 and P < 0.0001, respectively). In 15/21 patients who had an intercycle sFSH elevation, this was confirmed by uFSH elevation, both occurring within 2-4 days after stopping E2. In all these women, the sonogram showed evidence of impending ovulation. The amplitude of the uFSH signal was on average 3 times higher than its sFSH counterpart. In 6/21 women, no intercycle FSH elevation was detected and no ovulation occurred. DISCUSSION AND CONCLUSION: Our results show that the intercycle FSH signal can easily be identified and measured in urine. This novel approach permits more precise assessments of ovarian physiology than with blood measurements.

Adult↗

[Reproductive endocrinology and infertility in the light of 20 years of IVF experience].

In vitro fertilization (IVF)'s results have continuously improved over the past 20 years, making IVF part of routine services offered by most medical communities. The simplification of medical (ultrasound guided oocyte aspirations) and biological techniques (ready made media) contributed to the widespread development of IVF in the private sector, including in Switzerland. This challenges the needs of maintaining academic based IVF programs in the French speaking Switzerland. We believe however that IVF should remain part of academic gynecology because it also brings widespread collateral benefits that serve Gynecology notably, for teaching. Yet, the restricted size the French speaking Switzerland calls for creative approaches.

Endocrinology↗

[When should we treat infertility and how should we determine the degree of urgency?].

The successes of assisted reproductive treatments (ART) have been amply documented. Yet, there is no clear consensus as to who are the couples who need ART and with which degree of urgency, short of course of those suffering from definitive tubal infertility or severe male factor. Determining the degree of medical urgency for deploying ART approaches is of true clinical concern. In case of occult forms of ovarian failure (not symptomatic short of infertility itself), delaying treatment may lead to definitive failure. Conversely, if infertility results from ovulatory disorders brought by stress, postponing ART for a few months may bring spontaneous pregnancies. The recent introduction of anti-mullerian hormone (AMH) testing is of significant help for assessing the degree of ovarian reserve.

Female↗

[Menopause: where are we three years beyond WHI?].

The WHI triggered a great debate on Menopausal Hormonal Therapy. We now know that HT should not be used in cardio-vascular prevention. Many studies have yet been published regarding it's influence on breast cancers. Risks should be modulated in respect with the type of treatment and the targeted population. Only recently menopaused women or women suffering from invalidating menopausal symptoms should benefit from HT. When an HT is needed, the authors recommend the use of trans-cutaneous estrogens combined with natural oral progesterone. Every HT should be prescribed individually, according to the patient's aspirations and expectations.

Breast Neoplasms↗

[Use of aromatase inhibitors in infertile women].

Aromatase inhibitors (AI) block the last enzymatic step of estrogen production, the aromatization of the A-cycle of aromatizable androgens and particularly, androstenedione (D4) and testosterone (T). Molecules designed for interfering with aromatase activity have existed for many years. Yet the activity of products of the aminogluthetimide era was too unspecific and these substances carried too many side effects for being used clinically. Today, however, 3rd generation AIs have become available that are highly specific and essentially devoid of side effects. These molecules have recently been approved for treating breast cancer in post-menopausal women, either in advanced forms, or as part of adjuvant therapy. In women whose ovaries are active, a temporary inhibition of E2 production will activate gonadotropins and in turn, stimulate follicular growth. In cancer patients, this property precludes the use of AIs in women whose ovaries are still active, unless gonadotropins are blocked. In infertile patients, this property of AIs has been put to play for inducing ovulation. AIs have been used both in women who do not ovulate but whose hypothalamo-pituitary-gonadal (HPG) axis is active (oligo-anovulators of PCOD type) and in those who ovulate regularly but in whom multiple ovulation is sought for treating infertility or as part of IVF. Like CC, AIs are not usable in women whose gonadotropins are suppressed, as in the case of hypothalamic amenorrhea. The sum of data available on the use of AI for inducing ovulation remains however meager to this date and is mainly constituted of pilot and non-randomized trials. Yet mounting evidence tends to support AIs' advantages over CC for induction of ovulation. Hence, we think that these drugs will play a key role for the induction of ovulation in the future.

Anovulation↗

[Menorrhagia and hemostatic abnormalities: diagnosis and treatment].

Menorrhagias consisting of heavy menstrual bleeding are a common complaint, encountered in approximately 15% of women between the ages of 30 and 50. Diagnosis is difficult because women present different forms of excessive menses and no simple objective ways of measuring menstrual blood loss exist. A pictorial blood assessment chart was therefore validated for a better management of heavy menstrual bleeding. In half of the cases, no gynaecologic cause is found. Therefore, blood tests should be performed aiming at identifying coagulation disorders. We present here the results of our small series. Identification of coagulation disorders may allow specific treatments. These improve the quality of life and prevent unnecessary radical measures such as notably, hysterectomies.

Blood Coagulation Disorders↗

Effects of vaginal progesterone administration on uterine contractility at the time of embryo transfer.

OBJECTIVE: To investigate whether uterine contractility at the time of embryo transfer (ET) can be reduced by early onset of luteal support with progesterone administered vaginally. DESIGN: Prospective analysis. SETTING: Assisted reproduction unit. PATIENT(S): Eighty-four women undergoing 84 GnRH-a and FSH/hCG cycles for IVF-ET were studied. INTERVENTION(S): Vaginal progesterone was randomly started on the day of oocyte retrieval (group A, n = 43) or on the evening of ET (group B, n = 41). On the day of hCG administration and just before ET, 2-minute sagittal uterine scans were obtained by ultrasound and digitized with an image analysis system for assessing uterine contraction frequency. MAIN OUTCOME MEASURE(S): Uterine contraction frequency. RESULT(S): Whereas uterine contraction frequency was similar in both groups on the day of hCG (4.6 +/- 0.3 and 4.5 +/- 0.3 contractions per minute, respectively), only women in group A showed decreased uterine contraction frequency on the day of ET (2.8 +/- 0.2 vs. 4.2 +/- 0.3 contractions per minute). CONCLUSION(S): Vaginal progesterone administration starting on the day of oocyte retrieval induced a decrease in uterine contraction frequency on the day of ET as compared with preovulatory values. Uterine relaxation before ET is likely to improve IVF-ET outcome by avoiding the displacement of embryos from the uterine cavity.

Adult↗

Uterorelaxing effects of vaginal progesterone: comparison of two methodologies for assessing uterine contraction frequency on ultrasound scans.

OBJECTIVE: To assess the changes in uterine contractility induced by increasing doses of P administered to estrogenized women and to compare two methodologies for assessing uterine contraction frequency from ultrasound scans. DESIGN: Prospective double-blind parallel study. SETTING: Academic tertiary center. PATIENT(S): Infertile women aged 21-39 years with premature ovarian failure. INTERVENTION(S): P support set to duplicate the luteal phase was provided every 2 days by application of 1.125 g of Crinone 4% and 8% or 2.25 g of Crinone 8%, containing 45, 90, and 180 mg of P per application, respectively. MAIN OUTCOME MEASURE(S): Changes in uterine contraction frequency following exposure to three doses of vaginal P on ultrasound scans analyzed by visualizing accelerated image sequences and using a previously described three-dimensional (3D)-derived approach. RESULT(S): A decrease in uterine contraction frequency reached statistical significance on the third day of exposure to P without differences between the three dose groups. The two methods for measuring uterine contraction frequency on ultrasound scans were equivalent. CONCLUSION(S): At all three doses studied, the vaginal P gel Crinone administered to estrogenized women induced a profound decrease in uterine contraction frequency that duplicated the changes in contractility described in the luteal phase of the menstrual cycle. Analyzing uterine contraction frequency on accelerated image sequences is as effective as our more complex approach based on identifying contractions on time mode graphs electronically reconstructed using 3D-software.

Administration, Intravaginal↗

Human chorionic gonadotropin: does it affect human endometrial morphology in vivo?

Human chorionic gonadotropin (hCG) is widely used as a surrogate to luteinizing hormone (LH) to trigger ovulation in controlled ovarian hyperstimulation (COH). Yet this molecule may exert direct effects on the endometrium. These effects, not mediated by ovarian hormones, are probably a consequence of stimulation of endometrial hCG/LH receptors. Because the half-life of hCG differs markedly from that of LH, possible pharmacological effects of hCG on the endometrium could alter endometrial receptivity in COH. Arguments supporting a clinical action of gonadotropins, and hCG in particular, on the endometrium abound. Notably, evidence has been reported of decidualization of stromal cells of the human endometrium in vitro as a result of exposure to gonadotropins, including hCG. The present article discusses, from a clinical standpoint, the main basis supporting the hypothesis that hCG administration as commonly used in infertility treatments may exert direct effects in vivo on endometrial histology and partake in endometrial transformations of the luteal phase. Preliminary results suggest that endometrial effects of hCG exist in vivo and should be taken into account when assessing the endometrial effects of hormones.

Cells, Cultured↗

Uterine contractility: vaginal administration of the beta-adrenergic agonist, terbutaline. Evidence of direct vagina-to-uterus transport.

Spontaneous uterine contractility during the menstrual cycle is required for menstruation, gamete transport, and, most likely, embryo nidation. Abnormal uterine contractility has been linked to dysmenorrhea, a condition associated with painful uterine cramping. Based on previous studies with progesterone, we have postulated the existence of a portal system that is responsible for some degree of direct vagina-to-uterus transport of administered compounds (i.e., the "first uterine pass effect"). It is possible that treatment with uterorelaxing substances, particularly beta-adrenergic agonists, may alleviate the uterine discomfort that accompanies dysmenorrhea. However, side effects encountered with oral administration of beta-agonists limit their utility. Alternatively, vaginal delivery of beta-agonists could solve this dilemma by enhancing their efficacy and reducing side effects. Therefore, in the current study we used hysterectomy specimens and an in vitro uterine perfusion system to test the vagina-to-uterus transport of [3H]terbutaline, a well-known beta-agonist. With the use of autoradiographic and scintillation counting techniques, our results clearly show progressive diffusion of labeled terbutaline from the rim of vaginal tissue through the uterus during the first 12 hours of perfusion. This indicates that uterine targeting of terbutaline can be accomplished through vaginal administration, suggesting a new therapeutic modality in women's health care.

Administration, Intravaginal↗

Contractility of the nonpregnant uterus: the follicular phase.

Recent renewed interest in uterine contractility stems from the possibility of directly visualizing uterine contractility on images generated by high-resolution ultrasound probes. During the menstrual cycle, three typical patterns of uterine contractility have been recognized. During the luteofollicular transition and early follicular phase (menses), the contractile event involves all layers of the myometrium and exerts antegrade (from fundus to cervix) expulsive forces. Characteristically, uterine contractions are often perceived by women at the time of menses, sometimes reaching the level of painful cramps (dysmenorrhea). In the late follicular phase, uterine contractility involves only the subendometrial layers of the myometrium and is never perceived by women. The primary function of uterine contractility in the late follicular phase is to facilitate the retrograde (cervix to fundus) transport of sperm towards the distal end of the fallopian tubes where fertilization normally takes place. Finally, the uterus reaches a stage of quiescence after ovulation (under the influence of progesterone) that characterizes the major part of the luteal phase. The present review summarizes our understanding of the physiological role of uterine contractility during the follicular phase and the possible implications in pathological circumstances such as endometriosis and dysmenorrhea.

Endometriosis↗

New look at endometrial echogenicity: objective computer-assisted measurements predict endometrial receptivity in in vitro fertilization-embryo transfer.

OBJECTIVE: To determine whether endometrial echogenicity, assessed objectively by a computer-assisted system on the day of hCG administration, predicts endometrial receptivity in controlled ovarian hyperstimulation (COH) cycles for IVF-ET. DESIGN: Prospective analysis. SETTING: Assisted reproduction unit, Clamart, France. PATIENT(S): Two hundred twenty-one women (aged <38 years with a normal uterus and >/=2 grade A or B embryos transferred) undergoing 228 GnRH agonist and FSH/hCG cycles for IVF-ET. INTERVENTION(S): On the day of hCG administration, uterine ultrasound scans were digitized with an image analysis system. Endometrial echogenicity was assessed as the ratio of the extent of the hyperechogenic transformation over the whole endometrial thickness. According to this, cycles were sorted arbitrarily into six groups: <30% (n = 34), 31%-40% (n = 37), 41%-50% (n = 37), 51%-60% (n = 55), 61%-70% (n = 37), and >70% (n = 28). MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates. RESULT(S): The groups were similar in regard to population characteristics, ovarian response to COH, and embryology data. Pregnancy rates (59%, 57%, 35%, 20%, 16%, and 11%, respectively) and implantation rates (35%, 23%, 17%, 6%, 7%, and 3%, respectively) fell progressively and significantly from the low-echogenicity group to the high-echogenicity group. CONCLUSION(S): The present results confirm and extend previous observations that advanced hyperechogenic transformation of the endometrium is associated with poor IVF-ET outcome.

Adult↗

Human chorionic gonadotropin administration does not increase plasma androgen levels in patients undergoing controlled ovarian hyperstimulation.

OBJECTIVE: To investigate the effects of hCG administered to patients undergoing controlled ovarian hyperstimulation on levels of ovarian hormones, including androgens. DESIGN: Prospective analysis. SETTING: Assisted Reproduction Unit, Hôpital Antoine Béclère, Clamart, France. PATIENT(S): Six infertile, normally ovulating volunteers. INTERVENTION(S): The women underwent controlled ovarian hyperstimulation with a GnRH agonist and hMG for IVF-ET. After the i.m. administration of hCG (10,000 IU), blood samples were drawn every 6 hours for 4 days. MAIN OUTCOME MEASURE(S): Plasma androstenedione, testosterone, progesterone, and E2 profiles. RESULT(S): Treatment with hMG increased plasma androstenedione and testosterone levels 1.4-fold and 2.6-fold, respectively. The administration of hCG did not increase plasma androstenedione and testosterone levels any further; mean daily levels remained at 2.3 ng/mL and 0.64 ng/mL, respectively. Circadian changes in androstenedione levels were evident after hCG administration. Plasma progesterone levels neared 10 ng/mL 19 hours after hCG administration, plateaued for 24 hours, and increased again thereafter. Plasma E2 levels declined during the first 2 days after hCG administration and then increased, concomitant with the second phase of progesterone elevation. CONCLUSION(S): In patients undergoing controlled ovarian hyperstimulation, androgen levels increased in response to hMG treatment, but no further elevation occurred after hCG administration. The rate of elevation of progesterone levels and the absolute levels achieved were 3-fold and 10-fold higher, respectively, than those observed during spontaneous menstrual cycles.

Adult↗

Direct transport of progesterone from vagina to uterus.

OBJECTIVE: To compare progesterone concentrations in serum and endometrial tissue from hysterectomy specimens after vaginal or intramuscular (IM) administration of progesterone gel. METHODS: This was a randomized open study of 14 post-menopausal women undergoing transabdominal hysterectomies. Participants received either vaginal progesterone gel, 90 mg, or IM progesterone, 50 mg, at 8:00 AM and 8:00 PM on the day before surgery and at 6:00 AM on the day of surgery. Venous blood samples for progesterone measurement were collected at 8:00 AM on the day before surgery (baseline) and during surgery. After removal of the uterus, the endometrium was sampled from the anterior and posterior walls. Results were expressed as ratios of endometrial to serum progesterone concentrations x 100. RESULTS: Ratios of endometrial to serum progesterone concentrations were markedly higher in women who received vaginal progesterone (14.1 median, 8.5-59.4 range; 95% confidence interval [CI] 9.89, 38.79) compared with IM injections (1.2 median, 0.5-13.1 range; 95% CI -0.48, 7.39) (P < .005). CONCLUSION: Ratios of endometrial to serum progesterone concentrations were higher after vaginal administration of progesterone than after IM injections. Our findings in endometrial tissue specimens from hysterectomies excluded the possibility of contamination by progesterone that remained in the vagina.

Administration, Intravaginal↗

Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women.

OBJECTIVES: We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate (MPA) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infarction, or both. BACKGROUND: Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopausal women; however, women with an intact uterus also take progestin to protect against uterine malignancies. The effects of combination estrogen/progestin therapy on myocardial ischemia are unknown. METHODS: Eighteen postmenopausal women (mean +/- SD age 59+/-7 years) were given 17-beta-estradiol in single-blinded manner for four weeks (1 mg/day for three weeks then 2 mg/day for one week). Estradiol (2 mg/day) was then continued, and the patients were randomized (double-blind) for 12 days to either transvaginal progesterone gel (90 mg on alternate days) and oral MPA placebo (10 mg/day), or vice versa. After another two weeks on estradiol alone, the patients crossed over to progestin treatment and repeated the protocol on the opposite treatment. Patients underwent treadmill exercise testing after each estradiol phase and at day 10 of each progestin phase. RESULTS: Exercise time to myocardial ischemia increased after the first estrogen phase as compared with baseline (mean difference with 95% confidence interval [CI]: 72 s [34 to 110], p = 0.001), and was increased by combination estradiol/progesterone therapy as compared with estradiol/MPA therapy (92 s [35 to 149], p = 0.001)). Two patients (11%) were withdrawn while taking estradiol/MPA owing to unstable angina. CONCLUSIONS: Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia, as compared with estrogen/MPA. These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration.

Cross-Over Studies↗