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I Cédrin-Durnerin

Publications and source records attributed to I Cédrin-Durnerin.

17 recordsLinked to original sources

Effects of oral contraceptive, synthetic progestogen or natural estrogen pre-treatments on the hormonal profile and the antral follicle cohort before GnRH antagonist protocol.

BACKGROUND: Steroid pre-treatments may be useful to program GnRH antagonist IVF/ICSI cycles. This prospective study assessed hormonal and ultrasound data collected during the free period after the discontinuation of three different pre-treatments to provide information on the optimal time interval required before starting stimulation. METHODS: Women were randomized to receive oral contraceptive pill (OCP) [ethinyl estradiol (E(2)) 30 microg + desogestrel 150 microg] (n = 21) or norethisterone 10 mg/day (n = 23) or 17-betaE(2) 4 mg/day (n = 25) or no pre-treatment (n = 24) for one cycle before IVF. Assessments were performed on post-treatment day (PD) 1, 3 and 5, or on spontaneous cycle day (CD) 1 and 3. RESULTS: After OCP and progestogen administration, FSH and LH concentrations shifted from strongly suppressed PD1 levels to PD5 values similar to those observed on CD1. Meanwhile, follicle sizes remained small up to PD5. In contrast, estrogen pre-treatment poorly reduced FSH levels on PD1 compared with OCP or progestogen. Consequently, follicle size was more heterogeneous. FSH rebound was maximal on PD3, whereas LH levels were slightly increased up to PD5. CONCLUSIONS: A 5-day free interval after OCP or progestogen offers the advantages of gonadotrophin recovery and homogeneous follicular cohort, whereas early FSH rebound occurring after estrogen pre-treatment argues for a short free period.

Adult↗

The use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study.

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were <1200 pg/ml. The primary outcome measure was the number of follicles >or=16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation.

Anovulation↗

[Ovarian hyperstimulation syndrome: is there a place for surgery?].

Ovarian hyperstimulation syndrome is a iatrogenic complication that could happen during ovulation induction. Metabolic modifications can lead to a third sector and organic failure. Medical treatment, undertaken in first line, may be insufficient. In these cases, invasive treatment, using surgical techniques, in association with reanimation principles becomes necessary. From the simple drainage to final measures for the patient's rescue, this review describes the different solutions and their respective place. Several means exist, but serious evaluation is lacking. Their use should be indicated specifically. Medico-surgical associations seemed to offer interesting results.

Female↗

Recombinant human LH supplementation during GnRH antagonist administration in IVF/ICSI cycles: a prospective randomized study.

BACKGROUND: When administered in the late follicular phase to prevent an LH surge, GnRH antagonists induce a sharp decrease in serum LH levels that may be detrimental for assisted reproductive technology cycle outcome. Therefore, a prospective study was designed to assess the effects of recombinant human (r)LH supplementation during GnRH antagonist (cetrorelix) administration. METHODS: The protocol consisted of cycle programming with oral contraceptive pill, ovarian stimulation with rFSH and flexible administration of a single dose of cetrorelix (3 mg). A total of 218 patients from three IVF centres were randomized (by sealed envelopes or according to woman's birth date) to receive (n = 114) or not (n = 104) a daily injection of rLH 75 IU from GnRH antagonist initiation to hCG injection. RESULTS: The only significant difference was a higher serum peak E2 level in patients treated with rLH (1476 +/- 787 versus 1012 +/- 659 pg/ml, P < 0.001) whereas the numbers of oocytes and embryos as well as the delivery rate (25.2 versus 24%) and the implantation rate per embryo (19.1 versus 17.4%) were similar in both groups. CONCLUSIONS: These results show that in an unselected group of patients, there is no evident benefit to supplement GnRH antagonist-treated cycles with rLH.

Adult↗

[Intrauterine insemination: spontaneous or medically-assisted ovulation?].

Intrauterine insemination (i.u.i.) is usually proposed as the first-line therapy for infertility related to cervical factor, male and unexplained infertility. The overall success rate of i.u.i. is about 10-20% clinical pregnancies per cycle. i.u.i. may be performed in patients with or without prior controlled ovarian hyperstimulation (COH). The aim of COH is to closely monitor follicular growth in order to achieve a timely triggering of ovulation and i.u.i. Additionally, ovarian stimulation allows to increase the number of developing follicles. According to the review of previous prospective randomized studies and meta-analyses, it seems that: (i) when a cervical factor is involved, the advantage of COH in conjunction with i.u.i. is likely but has to be confirmed; (ii) in male infertility, COH with gonadotropins in conjunction with i.u.i. increases the clinical pregnancy rate by two. In this situation, the better the sperm parameters are, the more advantageous COH is; (iii) in unexplained infertility, COH in addition to i.u.i. improves the pregnancy rate but stimulation with clomifene citrate appears to be less effective than gonadotropins administration. Beside the sperm parameters, the success rate depends on both woman's age and degree of ovarian stimulation. Meanwhile, ovarian hyperstimulation exposes to the risk of multiple pregnancy and hyperstimulation syndrome. Increasing the number of preovulatory follicles from one to two allows to approximately double the pregnancy rate. However, there is clear evidence that getting three or more than three follicles exposes to a worrying risk of multiple pregnancy. At the present time, the successful outcome of i.u.i. should not be assessed by the clinical pregnancy rate any longer but by the singleton birth rate. Our therapeutic strategy for COH prior to i.u.i. should take into account woman's age, infertility duration and associated infertility factors. The objective in terms of preovulatory follicle number must be determined prior to the stimulation in order to optimise the cycle outcome with a singleton birth.

Adult↗

[Antagonist protocols: residual LH levels and the value of exogenous LH supplementation].

When administered in the late follicular phase to prevent any LH surge, GnRH antagonists induce a sharp decrease in serum LH levels that may be detrimental for assisted reproductive technology cycle outcome. This decrease in LH levels is dose-dependant. Supplementation with recombinant LH when introducing GnRH antagonist leads to significant changes in E2 secretion. This is consistent with a key role of LH to ensure adequate steroidogenesis. This also indicates that a single dose of GnRH antagonist is able to decrease bioactive LH below a minimal threshold for optimal steroidogenesis. However, supplementation with rLH does not modify the number of retrieved oocytes, obtained embryos and the pregnancy rate. This is in line with the concept that folliculogenesis is mainly dependent on FSH and that the role of LH and E2 is not primordial. Indeed, the findings of our prospective randomized study do not support a systematic supplementation with rLH when introducing antagonist. However, further studies are necessary to determine whether a specific sub group of patients characterized by a low E2/oocyte ratio could benefit from rLH supplementation.

Adult↗

[Oocytes in vitro maturation: results and future in humans].

Mature oocytes are rare and highly specialized cells. In vitro maturation of human oocytes is an emerging assisted reproductive technology allowing to produce more mature oocytes without ovarian stimulation. Whereas in vitro maturation is technically more demanding than conventional in vitro fertilization for the laboratory, it carries many potential advantages, for example, in terms of lower treatment heaviness and removal of risk of severe ovarian hyperstimulation syndrome for the patients. Although the technology is still experimental, oocytes in vitro maturation has been successfully used and pregnancies and live births have been reported. Despite these successes, the overall efficiency of in vitro maturation remains low and this procedure must still be improved. The different steps of in vitro maturation process are shown and discussed as well as results in terms of pregnancy and live birth rates.

Cell Culture Techniques↗

[Should infertile women with polycystic ovarian syndrome be treated with metformine?].

Polycystic ovary syndrome is a frequent endocrine disorder often associated with insulin resistance and hyperinsulinaemia which may play a role in hyperandrogenism and anovulation. The use of "insulin sensitizing" agents has been suggested to reduce insulin resistance and hyperandrogenism. In that respect, the use of metformin in polycystic ovary syndrome is reviewed. Although its mechanism of action is still unclear, metformin proved to be effective to restore cyclicity and spontaneous ovulation. The synergistic effect of clomiphene citrate and metformin was demonstrated in some studies, suggesting that metformin could be helpful for women with clomiphene citrate resistance. However, the potential effect of metformin administration for reducing hyperstimulation in women treated with exogenous FSH, or for preventing early miscarriages has to be confirmed. Here, we propose a guideline for the use of metformin, as an adjuvant therapy, to restore cyclicity and ovulation in women with polycystic ovary syndrome.

Clomiphene↗

Beneficial effects of GnRH agonist administration prior to ovarian stimulation for patients with a short follicular phase.

A short follicular phase is an early clinical feature of declining reproductive competence. The shortening of the follicular phase length is related to both advanced recruitment and selection of the dominant follicle secondary to an earlier and higher FSH rise during the luteal-follicular transition, while the late follicular growth is normal. As a short follicular phase may be detrimental for reproduction, it was postulated that increasing the duration of follicular phase could improve conception rate. For that purpose, gonadotrophin-releasing hormone agonist minidoses were administered in the mid-luteal phase to prevent the intercycle FSH rise before tailoring follicular growth by controlled exogenous FSH administration. This regimen, applied to 69 infertile ovulatory women with a short follicular phase (9.6 +/- 1.2 days) actually lengthened the follicular phase by about 3 days. It proved to be effective in 179 cycles to induce paucifollicular development (1.8 +/- 0.9 follicles) with a low cancellation rate (4%) and a moderate requirement for gonadotrophins [13.3 +/- 6.3 ampoules (75 IU)]. In those women with a high frequency (80%) of elevated basal FSH or oestradiol concentrations, the pregnancy rate reached 15.1%/cycle but the miscarriage rate remained high (44%). Thus, increasing the follicular phase length in patients with a short follicular phase may partially restore fecundity.

Adult↗

[Benefits and risks of ovarian stimulation before intrauterine insemination].

Performance of intra-uterine insemination (IIU) is generally advocated as a first line therapy for infertility related to cercical hostility, male factor, unexplained infertility or mild endometriosis. IIU are usually performed following stimulation of ovulation, even in absence of anovulation. However the rationale for such a systematic ovulation induction is still questionable. Indeed, while an overall assessment of ovarian stimulation tends to conclude to a beneficial effect of these treatments in unexplained or some male infertility, it is clear that no definitive conclusion can be drawn. Indeed, the methodology in many published series is mostly inadequate, data are usually not analysed according to the type of infertility or to the female hormonal features. Finally, adverse effects are imperfectly descripted. A more accurate analysis of these data in relation to the number of recruited follicles definitively shows that, if a bifollicular development is associated with a significant increase in the pregnancy rates, there is no advantage to stimulate further the ovary. Indeed, surpassing the recruitment of two follicles would lead to dramatically increase the risk of OHSS and multiple pregnancies. Thus, further investigations including prospective, randomized studies are needed to better define what should be the most adequate regimen of ovulation induction. Specifically, tailoring the rate of multifollicular development according to the duration, the type of infertility (etiology; primary or secondary; female age) would prove to be a safer approach for getting pregnancy as well as avoiding adverse effects. Such a policy remains to be determined in the light of further clinical studies conducted in the more appropriate manner.

Female↗

Effectiveness of low dose of gonadotropin releasing hormone agonist on hormonal flare-up.

PURPOSE: The hormonal response (flare-up) following administration of a standard dose (100 micrograms) or a low dose (25 micrograms) of gonadotropin releasing hormone agonist (GnRH-a) (Triptorelin) was compared in patients prior to an in vitro fertilization (IVF) cycle and during the early follicular phase of a short-term IVF protocol. METHODS: The gonadotroph (FSH, LH) and steroid [estradiol (E2) and progesterone (P)] flare-up was studied on two consecutive cycles in 30 normo-ovulatory women. Patients were randomized to receive either 25 or 100 micrograms of triptorelin for three days at the beginning of the first cycle. Then doses were switched according to a crossing over design in the second cycle. RESULTS: No significant difference in the magnitude of FSH and E2 release could be observed following administration of the two doses of agonist whereas maximal plasma LH level was significantly reduced after injection of 25 micrograms of triptorelin. CONCLUSIONS: As compared to a standard dose, using a low dose of GnRH-a induces an hormonal flare-up which seems adequate for an optimal follicular recruitment.

Adult↗

[Revisiting GnRH analog protocols II. Strategy for poor responders].

In the first part of this review, we analyzed protocols for ovarian hyperstimulation with GnRH analogs and stressed both their diversity and uncertainty for mechanisms which lead to improve the outcome of IVF cycles. Apart from their beneficial effects on prevention of endogenous LH surges and premature luteinization, other adverse effects have been reported: need of higher amount of exogenous gonadotrophins, direct negative action on ovarian function and conceptus quality. They must be considered before defining a strategy for poor responders to IVF protocols using GnRH analogs. The recent trend for reducing GnRH doses must be evaluated.

Animals↗

Sequential step-up and step-down dose regimen: an alternative method for ovulation induction with follicle-stimulating hormone in polycystic ovarian syndrome.

This study was designed to compare both the effectiveness and safety of two low-dose gonadotrophin regimens (step-up versus sequential step-up and step-down) for ovulation induction in polycystic ovarian syndrome (PCOS) patients. In all, 56 infertile clomiphene citrate-resistant PCOS patients were included in this prospective randomized study. A total of 38 cycles were conducted with a classic step-up protocol, whereas for 35 cycles the follicle-stimulating hormone (FSH) threshold dose was reduced by half when the leading follicle reached 14 mm in diameter (sequential protocol). Serum oestradiol, progesterone and luteinizing hormone concentrations and follicular growth rate were evaluated during the cycle. At the time of human chorionic gonadotrophin administration, cycles treated with sequential protocol exhibited significantly lower oestradiol concentrations [434 +/- 45 versus 593 +/- 67 pg/ml (mean +/- SEM)] and the number of medium-sized (14-15 mm) follicles was significantly reduced (0.3 +/- 0.1 versus 0.8 +/- 0.2) compared with cycles treated with the classic step-up protocol. Moreover, in these cycles serum luteal oestradiol concentrations were decreased significantly (350 +/- 77 versus 657 +/- 104 pg/ ml) compared with the classic step-up protocol. A sequential step-up and step-down protocol seems to be a safe and effective regimen for ovulation induction in PCOS patients. Decreasing the FSH dose following step-up follicular selection may be an alternative method to avoid multifollicular development.

Adult↗

The hormonal flare-up following gonadotrophin-releasing hormone agonist administration is influenced by a progestogen pretreatment.

In a short-term protocol, the influence of progestogen pretreatment upon the oestradiol flare-up (delta E2) induced by gonadotrophin-releasing hormone agonist (GnRHa) was assessed in relation to in-vitro fertilization (IVF) outcome in 90 cycles programmed (n = 52) or not (n = 38) by norethisterone (10 mg/day for 12-20 days). Patients pretreated by progestogen had a significantly lower delta E2 value than patients without pretreatment (delta E2 = 26 +/- 5 versus 61 +/- 8 pg/ml, P = 0.003). It could be related to a lower gonadotrophic response for luteinizing hormone (LH) (delta LH = 9 +/- 0.8 versus 14.5 +/- 2.2 IU/l, P = 0.01). The IVF outcome (final oestradiol, number of oocytes or embryos) was similar in both groups and delta E2 was well correlated with these final parameters in each group. A significant rise in serum progesterone was observed only in patients without pretreatment (delta P = 1.1 +/- 0.2 versus 0.1 +/- 0.1 ng/ml, P < 0.0001). Thus norethisterone pretreatment decreases the oestradiol flare-up and prevents the early increase of progesterone (by avoiding some rescue of the corpus luteum or some luteinization of small developing follicles) but does not influence the outcome of the IVF cycle. In clinical practice, evaluation of the hormonal flare-up for predicting IVF outcome must take into account any pretreatment prescription.

Adult↗

[Evaluation of ovarian sensitivity to gonadotrophins: role of ovarian reserve tests].

Among several parameters involved in the age-dependent reduction in conception rate, intra-ovarian factors, specially the follicular oocyte complex, play a major role. The aim of endocrine challenge tests is to assess ovarian follicular reserve. Basal serum FSH determination on day 3 of the cycle is easily measurable, inexpensive. Its sensitivity is increased with a clomiphene citrate challenge test. Both GnRH agonist stimulation test and exogenous FSH test allow to evaluate more directly the ovarian function. However they are more invasive, expensive and need further standardisation.

Clomiphene↗

Progestogen pretreatment in the short-term protocol does not affect the prognostic value of the oestradiol flare-up in response to a GnRH agonist.

The prognostic value of the oestradiol flare-up in response to gonadotrophin-releasing hormone (GnRH) agonist was evaluated in 140 in-vitro fertilization (IVF) cycles programmed by progestogen pretreatment. Three days after the end of administration of norethisterone, a routinely used short-term DTRP6 GnRH agonist protocol was started (designated day 1), gonadotrophins being introduced from day 4. Serum oestradiol flare-up values were evaluated on days 1, 2 and 3 to study their relationship with the subsequent IVF outcome. On day 2, 87.9% of the cycles exhibited a significant rise in serum oestradiol concentration from baseline (delta E2 > or = 5 pg/ml). Compared to cycles without any significant oestradiol increase, they had a higher pregnancy rate per transfer (33.3 versus 9.1%, P = 0.02), although the number of transferred embryos did not differ significantly. Taking into account the previously described cut-off value (doubling from baseline), we found that less than half of the cycles (45.7%) involved a doubling of oestradiol values during flare-up, and we did not observe any significant difference in IVF outcome in these cycles compared to those without doubling. In conclusion, progestogen pretreatment, by inducing ovarian quiescence, may lower the oestradiol cut-off value that is predictive of the subsequent pregnancy rate. Nevertheless, determination of the absolute oestradiol response (delta E2) to GnRH agonist after progestogen pretreatment could allow a further adaptation of the protocol to achieve an optimum response in each cycle. Another alternative for patients with a lower delta E2 could be the suppression of progestogen pretreatment.

Adult↗