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Efstratios M Kolibianakis

Publications and source records attributed to Efstratios M Kolibianakis.

At least 19 recordsLinked to original sources

Human chorionic gonadotropin administration vs. luteinizing monitoring for intrauterine insemination timing, after administration of clomiphene citrate: a meta-analysis.

OBJECTIVE: To systematically compare hCG administration as a method for intrauterine insemination (IUI) timing with conservative urinary LH surge detection in infertility treatment. DESIGN: Meta-analysis of prospective and retrospective trials. SETTING: Tertiary fertility and IVF center. PATIENT(S): One thousand four hundred sixty-one patients who received hCG after a clomiphene citrate regimen, compared with 1,162 patients who had an LH surge detection for IUI timing. INTERVENTION(S): Both MEDLINE and Cochrane Collaboration were searched. References of retrieved articles were included in the search. The meta-analysis included all controlled trials examining the effectiveness of hCG administration before IUI on clinical-pregnancy rates in comparison with LH detection. Two independent reviewers performed data extraction. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): Seven studies with 2,623 patients were included in the meta-analysis (1,461 patients received hCG, and 1,162 had LH surge detection). When all studies were combined, patients who received hCG before IUI demonstrated lower clinical-pregnancy rates than did women who had IUI after spontaneous ovulation (odds ratio, 0.74; 95% confidence interval, 0.57-0.961). In subgroup analysis of studies that considered ovulatory dysfunction to be the infertility reason, the results favored women who received hCG. In contrast, across studies that reported male factor as the infertility reason, as well as across studies including women with unexplained infertility, results appeared to favor the LH surge detection approach. However, none of those subgroup analyses reached statistical significance. CONCLUSION(S): Available data do not demonstrate a consistent, clinically important benefit of hCG-induced ovulation compared with spontaneous ovulation for IUI timing.

Adult↗

The luteal phase of recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in vitro fertilization cycles during supplementation with progesterone or progesterone and estradiol.

OBJECTIVE: To explore luteal phase hormone profiles in patients stimulated with recombinant FSH and GnRH antagonist for IVF under two different modes of luteal support: P and P with E(2). DESIGN: Prospective randomized study. SETTING: Patients in an academic reproductive medicine unit. PATIENT(S): One hundred and three patients undergoing ovarian stimulation with a fixed dose of 200 IU recombinant FSH and GnRH antagonist. INTERVENTION(S): Patients were randomized to receive luteal phase supplementation, either P vaginally (n = 49) or P and 4 mg E(2) orally (n = 54). MAIN OUTCOME MEASURE(S): Hormonal assessment during the luteal phase on days 1, 4, 7, and 10 after the administration of hCG. RESULT(S): Hormone levels did not differ during the luteal phase between the two groups with the exception of E(2) concentration on day 10 after hCG, which was significantly higher in the E(2)-supplemented group compared with the P group (median 760 pg/mL, range 2,496 vs. median 589.50 pg/mL, range 2,098). CONCLUSION(S): Addition of 4 mg E(2) for luteal support after stimulation with recombinant FSH and GnRH antagonist does not alter significantly the endocrine profile of the luteal phase until day 7 after hCG. At day 10 after hCG, the E(2) levels are significantly higher in the E(2)-supplemented group.

Adult↗

In vitro fertilization with single blastocyst-stage versus single cleavage-stage embryos.

BACKGROUND: Single-embryo transfer has been recommended to reduce the incidence of multiple gestations when in vitro fertilization is performed in women under 36 years of age. We designed a prospective, randomized, controlled trial to determine whether there were any differences in the rates of pregnancy and delivery between women undergoing transfer of a single cleavage-stage (day 3) embryo and those undergoing transfer of a single blastocyst-stage (day 5) embryo. METHODS: We studied 351 infertile women under 36 years of age who were randomly assigned to undergo transfer of either a single cleavage-stage embryo (176 patients) or a single blastocyst-stage embryo (175 patients). Multifollicular ovarian stimulation was performed with a gonadotropin-releasing hormone antagonist and recombinant follicle-stimulating hormone. RESULTS: The study was terminated early after a prespecified interim analysis (which included 50 percent of the planned number of patients) found a higher rate of pregnancy among women undergoing transfer of a single blastocyst-stage embryo (P=0.02). The rate of delivery was also significantly higher in this group than in the group undergoing transfer of a single cleavage-stage embryo (32.0 percent vs. 21.6 percent; relative risk, 1.48; 95 percent confidence interval, 1.04 to 2.11). Two multiple births occurred, both of monozygotic twins, both of which were in the group undergoing transfer of a single cleavage-stage embryo. CONCLUSIONS: These findings support the transfer of a single blastocyst-stage (day 5) embryo in infertile women under 36 years of age.

Adult↗

Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles.

OBJECTIVE: To determine the incidence of ovarian hyperstimulation syndrome (OHSS) in a large series of GnRH antagonist-stimulated cycles and to assess the predictive value of E2 and the number of follicles on the day of hCG administration. DESIGN: Prospective cohort study of women undergoing IVF treatment with a GnRH antagonist protocol over a 2-year period. SETTING: Tertiary university hospital. PATIENT(S): One thousand eight hundred one patients who underwent 2,524 cycles. INTERVENTION(S): Multifollicular ovarian stimulation with recombinant FSH and GnRH antagonist for IVF-ICSI treatment. MAIN OUTCOME MEASURE(S): Incidence of OHSS in GnRH antagonist cycles, predictive value of E2, and number of follicles on the day of hCG for OHSS occurrence. RESULT(S): Fifty-three patients were hospitalized because of OHSS (2.1%; 95% confidence interval [CI]:1.6-2.8). Early OHSS presented in 31 patients (1.2%; 95% CI: 0.9-1.8), whereas the late type was a complication in 22 patients (0.9%; 95% CI: 0.5-1.3). Late OHSS cases compared with the early OHSS cases always occurred in a pregnancy cycle (100% vs. 40%); had higher probability of being severe (72.7% vs. 42%), and more often were related to a multiple pregnancy (40% vs. 0). Receiver operating characteristic curve analysis for several E2 concentrations and number of follicles with a diameter of > or =11 mm revealed that the predictive value of the optimal threshold of > or =13 follicles (85.5% sensitivity; 69% specificity) was statistically significantly superior to the optimal threshold of 2,560 ng/L for E2 concentrations (53% sensitivity, 77% specificity) in identifying patients at risk for OHSS. Considering that severe OHSS represents the most clinically significant pattern, the combination of a threshold of > or =18 follicles and/or E2 of > or =5,000 ng/L yields a 83% sensitivity rate with a specificity as high as 84% for the severe OHSS cases. CONCLUSION(S): Clinically significant OHSS still remains a limitation of multifollicular ovarian stimulation for IVF even with the use of GnRH antagonist protocols. The number of follicles can discriminate the patients who are at risk for developing OHSS, whereas E2 concentrations are less reliable for the purpose of prediction. There is more than ever an urgent need for alternative final oocyte maturation-triggering medication.

Adult↗

Menstruation-free interval and ongoing pregnancy in IVF using GnRH antagonists.

BACKGROUND: The purpose of this study was to evaluate prospectively the association between the achievement of ongoing pregnancy and the time interval from the end of menstruation until the administration of HCG (menstruation-free interval) in patients treated by IVF. METHODS: A fixed dose of 200 IU of recombinant FSH (rFSH) was started in 90 patients on day 2 of the menstrual cycle and daily GnRH antagonist was initiated on day 6 of stimulation. Triggering of final oocyte maturation was performed with 10,000 IU of HCG as soon as three follicles of > or =17 mm were present at ultrasound. RESULTS: Single embryo transfer was performed in 64.6% of the patients who reached embryo transfer (53/82). Ongoing pregnancy rate per embryo transfer was 18.3% (95% CI 11.4-28.0%). The menstruation-free interval significantly predicted the probability of ongoing pregnancy in a logistic regression analysis, controlling for female age and LH on day 1 of stimulation (odds ratio for the menstruation-free interval: 0.70; 95% CI: 0.54-0.92). CONCLUSION: The longer the interval from the end of menstruation until the administration of HCG, the lower the probability of ongoing pregnancy in patients stimulated with recombinant FSH and GnRH antagonist for IVF.

Adult↗

Effect of oral contraceptive pill pretreatment on ongoing pregnancy rates in patients stimulated with GnRH antagonists and recombinant FSH for IVF. A randomized controlled trial.

BACKGROUND: The objective of this randomized controlled trial was to assess the effect of oral contraceptive pill (OCP) pretreatment on the probability of ongoing pregnancy in patients treated with a GnRH antagonist for IVF. METHODS: A fixed dose of 200 IU recombinant FSH (rFSH) was started in 425 patients either on day 2 of the menstrual cycle (non-OCP group: n = 211) or 5 days after discontinuing the OCP (OCP group: n = 214). GnRH-antagonist was initiated on day 6 of stimulation, and triggering of final oocyte maturation was performed with 10,000 IU of HCG. RESULTS: Ongoing pregnancy rates per started cycle in the non-OCP and OCP group were 27.5% and 22.9%, respectively [95% confidence interval (CI) of the difference: -3.7 to +12.8]. Pregnancy loss was significantly increased in the OCP (36.4%) compared with the non-OCP group (21.6%) (95% CI of the difference: -28.4 to -2.3). CONCLUSION: Pretreatment with OCP, as compared with initiation of stimulation on day 2 of the cycle in patients treated with GnRH antagonist and recombinant FSH, appears to be associated with a not significant difference in ongoing pregnancy rates per started cycle and results in a significantly higher early pregnancy loss.

Adult↗

Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH antagonist cycles.

BACKGROUND: Prolongation of follicular phase by delaying hCG administration has been reported to result in a significantly lower ongoing pregnancy rate that did not seem to be due to an embryonic factor. The aim of this prospective randomized study was to assess the effect of delaying hCG administration on endometrial histology. METHODS: Ten oocyte donors underwent endometrial biopsy on the day of oocyte retrieval and endometrial histology was assessed by Noyes' criteria. Ovarian stimulation was performed with recombinant (r)FSH and daily GnRH antagonist starting on day 6 of stimulation. Patients were randomized by a computer-generated list to receive 10 000 IU of hCG either as soon as > or =3 follicles > or =17 mm were present on ultrasound (early-hCG group, n = 5) or 2 days after this criterion was met (late-hCG group, n = 5). RESULTS: When hCG was delayed, endometrial advancement was present in all samples examined (median advancement 3 days, range 2-3 days). On the contrary, no secretory changes were observed when the follicular phase was not prolonged (difference in the proportion of patients with advancement between the early-hCG and the late-hCG group: 100%, 95% CI: 38-100). CONCLUSIONS: Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH antagonist cycles.

Adult↗

GnRH antagonists in IVF.

The present review summarizes existing knowledge on the use of gonadotropin releasing hormone (GnRH) antagonists based on experience gathered after the completion of phase III comparative trials with GnRH agonists. Available data suggest that prolongation of the follicular phase significantly decreases the probability of pregnancy. Moreover, patients with elevated progesterone at initiation of stimulation have significantly fewer chances of achieving an ongoing pregnancy. Luteal support remains mandatory, while the replacement of human chorionic gonadotrophin by GnRH agonist does not appear to be feasible. Although not conclusive, existing data are not in favour of increasing the starting dose of gonadotrophins, of LH supplementation or of using a flexible antagonist protocol.

Dose-Response Relationship, Drug↗

Estrogen and folliculogenesis: is one necessary for the other?

PURPOSE OF REVIEW: During folliculogenesis the primordial follicle undergoes several steps of maturation in order to develop into a preovulatory follicle. The exact role of estrogen during this process has not yet been fully assessed. RECENT FINDINGS: Estrogen appears to regulate cyclic gonadotropin release via its action on estrogen receptor alpha in the hypothalamus/hypophysis axis and to enhance folliculogenesis through its actions via estrogen receptor beta in the ovary. In addition, a role of estrogen during the very early stages of folliculogenesis is possible. However, it is likely that oocyte quality and developmental potential are not estrogen dependent. This might explain the lack of association between estrogen and in-vitro fertilization outcome in humans. SUMMARY: The advent of knockout mice models has enhanced our understanding of the role of estrogen during folliculogenesis. Existing data suggest that estrogen might be involved in the very early steps of this process, but its role in sustaining ovulation is mainly central.

Animals↗

Association of estradiol levels on the day of hCG administration and pregnancy achievement in IVF: a systematic review.

BACKGROUND: Evaluation of the association between estradiol (E2) levels on the day of hCG administration and pregnancy achievement in IVF has so far yielded conflicting results. The purpose of the present study was to systematically review the above association in cycles down-regulated with GnRH analogues. METHODS: Literature search was performed using Medline, Embase (1978-2004) and the Cochrane Library. Additionally, references of retrieved articles were hand-searched. Only full articles published in peer-reviewed medical journals were considered for analysis. RESULTS: All the eligible studies (n=9) involved the use of GnRH agonists and were retrospective. Two studies (including 191 patients) suggested that the higher the E2 levels on the day of hCG administration, the higher the probability of pregnancy. However, five studies (including 1875 patients), did not support an association between E2 levels on the day of hCG administration and pregnancy rates. Moreover, two of the studies including (1286 patients) suggested that high E2 levels on the day of hCG administration are associated with a decreased probability of pregnancy. If we consider only studies in which criteria used for administering hCG include follicular development but not E2 levels (including 2687 patients), there is no study suggesting a positive association between E2 levels on the day of hCG administration and pregnancy achievement. CONCLUSIONS: Currently there is no high-quality evidence to support or deny the value of E2 determination on the day of hCG administration for pregnancy achievement in IVF cycles, where pituitary down-regulation is performed with GnRH agonists. Existing retrospective studies suggest that there is no positive association. However, in order to arrive at recommendations for clinical practice, there is a need to perform well-designed prospective studies in both agonist and antagonist cycles.

Chorionic Gonadotropin↗

Administration of gonadotropin-releasing hormone antagonist from day 1 of stimulation in in vitro fertilization.

After administration of GnRH antagonist from day 1 of stimulation for IVF, 12.1 cumulus oocyte complexes were retrieved (95% confidence interval [CI], 10.6-13.6), 1.9 embryos were transferred (95% CI, 1.7-2.0), and 2.4 embryos were cryopreserved (95% CI, 1.7-3.1). Stimulation for 8.8 days (95% CI, 8.4-9.2) with recombinant FSH resulted in an ongoing implantation rate of 26.5% (95% CI, 17.1-35.9) and an ongoing pregnancy rate of 39.7% per started cycle (95% CI, 30.1-50.8) and of 42.4% per ET (95% CI, 32.3-53.1).

Adult↗

Prolongation of the follicular phase in in vitro fertilization results in a lower ongoing pregnancy rate in cycles stimulated with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonists.

OBJECTIVE: To assess the effect of altering the timing of hCG administration on ongoing pregnancy rates in patients stimulated with recombinant FSH (rec-FSH) and GnRH antagonists for IVF. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary referral center. PATIENT(S): Four hundred thirteen patients undergoing IVF. INTERVENTION(S): Rec-FSH stimulation starting on day 2 of the cycle combined with daily GnRH antagonist starting on day 6 of stimulation. Patients were randomized to receive 10000 IU of hCG either as soon as at least three follicles were >or=17 mm on ultrasound (early-hCG group, 208 patients) or 2 days later after this criterion was met (late-hCG group, 205 patients). MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate. RESULT(S): Fertilization rates and number and quality of embryos transferred did not differ between the two groups. However, a significantly lower ongoing pregnancy rate was present in the late-hCG as compared with the early-hCG group (25.0% vs. 35.6%, respectively). CONCLUSION(S): Prolongation of the follicular phase in patients stimulated with rec-FSH and GnRH antagonists for IVF does not affect oocyte or embryo quality but is associated with a significantly lower ongoing pregnancy rate.

Adult↗

Live delivery rates in subfertile women with Asherman's syndrome after hysteroscopic adhesiolysis using the resectoscope or the Versapoint system.

The purpose of this study was to report on a 10-year experience in the treatment of subfertile women with intrauterine adhesions using the resectoscope or the Versapoint system. Forty-six subfertile women with stage I (n = 6), stage II (n = 25) and stage III (n = 15) intrauterine adhesions underwent adhesiolysis with the use of the resectoscope (n = 21) or the Versapoint system (n = 26). Synechiolysis was successful in 43 women (93.5%) after the first attempt. In 13 out of 14 women (92.9%) with oligo/amenorrhoea at presentation, restoration of menses was reported after adhesiolysis (Versapoint: 9/9, resectoscope: 4/5). Overall live delivery rates according to stage of intrauterine adhesions were 33.3, 44.4 and 46.7% for stages I, II and III respectively. Similar cumulative delivery rates were achieved in patients with no additional infertility factors who attempted to conceive naturally after adhesiolysis using the Versapoint (71.7%) or the resectoscope (60%). Ten gestations ended in preterm delivery (50%), while in two of the women who delivered, a hysterectomy was performed due to placenta accreta. In conclusion, hysteroscopic adhesiolysis offers a real chance of parenthood in a substantial proportion of infertile couples either by using the Versapoint system or the resectoscope.

Adult↗

Ovarian stimulation for in vitro fertilization in patients with endometriosis.

The use of gonadotropin-releasing hormone (GnRH) agonists in a long protocol appears to enhance the probability of conception in the presence of endometriosis. In addition, there is evidence to suggest that the use of prolonged downregulation with GnRH agonists prior to ovarian stimulation for in vitro fertilization (IVF) is beneficial for achieving pregnancy. Until now, GnRH antagonists have not been used in patients with endometriosis. The management of endometriomas prior to stimulation for IVF and its impact on reproductive outcome are still subject to debate.

Adult↗

Outcome for donors and recipients in two egg-sharing policies.

OBJECTIVE: To assess the effect of two different donation policies on results of egg-sharing. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENT(S): One hundred five donor-recipient pairs participating in an egg-sharing program between 1998 and 2001. INTERVENTION(S): Egg-sharing was performed according to policy A (retrieval of at least 12 oocytes, with more oocytes allocated to the donor) or policy B (retrieval of at least 8 oocytes, with equal distribution of oocytes between donors and recipients). MAIN OUTCOME MEASURE(S): Delivery rate and cycle cancellation rate. RESULT(S): Policy B resulted in a decreased cycle cancellation rate in the recipient group compared with policy A (9.7% vs. 29.7%, respectively; P<or=.01). No significant difference in delivery rate per fresh transfer was observed between policy A and policy B in donors (30.2% vs. 27.8%, respectively) or recipients (28.2% vs. 25.7%, respectively). CONCLUSION(S): Decreasing the number of oocytes required to perform egg sharing from 12 to 8 and dividing the oocytes equally between donors and recipients significantly reduces the cycle cancellation rate while it does not appear to affect adversely the probability of delivery.

Adult↗

Exposure to high levels of luteinizing hormone and estradiol in the early follicular phase of gonadotropin-releasing hormone antagonist cycles is associated with a reduced chance of pregnancy.

OBJECTIVE: To compare ongoing implantation rates under two different GnRH antagonist protocols. DESIGN: Randomized controlled trial. SETTING: Tertiary referral center. PATIENT(S): One hundred eleven women undergoing ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). INTERVENTION(S): Ovarian stimulation with 150 IU recombinant-FSH (rec-FSH) starting on day 2 of the cycle and GnRH antagonist starting either on day 6 of stimulation (fixed group) or when a follicle of > or = 15 mm was present after at least 5 days of stimulation (flexible group). In the flexible group, the rec-FSH dose was increased to 250 IU when the antagonist was initiated. MAIN OUTCOME MEASURE(S): Ongoing implantation and pregnancy rate. RESULT(S): In patients with no follicle of > or = 15 mm present on day 6 of stimulation, a significantly lower ongoing implantation rate was observed if the flexible scheme was applied as compared with the fixed scheme of administration (8.8% vs. 23.9%, respectively). Exposure of the genital tract to LH or E2 from initiation of stimulation to antagonist administration was able to distinguish between pregnant and nonpregnant patients in the population studied. CONCLUSION(S): High exposure of the genital tract to LH and E2 in the early follicular phase is associated with a reduced chance of pregnancy in cycles stimulated with recombinant FSH and GnRH antagonist for IVF/ICSI.

Adult↗