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Biomedical subjects

E M Kolibianakis

Publications and source records attributed to E M Kolibianakis.

At least 19 recordsLinked to original sources

GnRH agonists vs antagonists.

Gonadotropin-releasing hormone (GnRH) agonists were introduced in ovarian stimulation for in-vitro fertilization to suppress the premature surge of luteinizing hormone (LH). Although agonist use is accompanied by a series of disadvantages, including hypoestrogenaemia, cyst formation, a requirement for a prolonged period of downregulation, and an increase in follicle-stimulating hormone (FSH) and LH as soon as the agonist is administered, agonists became well accepted in clinical practice as their use was also associated with increased rates of pregnancy. However, the recent development of side-effect-free GnRH antagonists, characterized by an immediate mode of action and a shorter period of administration. Provides clinicians with flexibility in terms of administration, and offers patients a friendlier method of ovarian stimulation. Comparative studies between the two analogues have suggested that the use of antagonists is associated with a shorter duration of FSH stimulation and a decreased incidence of hospital admission due to the occurrence of ovarian hyperstimulation syndrome, while the probability of a live birth does not depend on the type of analogue used.

Clinical Trials as Topic↗

Among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to answer the following clinical question: among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth per randomized patient dependent on the type of analogue used? Eligible studies were randomized controlled trials (RCTs), published as a full manuscript in a peer-reviewed journal, that contained sufficient information to allow ascertainment of whether randomization was true and whether equality was present between the groups compared. A literature search identified 22 RCTs comparing GnRH antagonists and GnRH agonists that involved 3176 subjects. Where live birth was not reported in a study that fulfilled the inclusion criteria, an effort was made to contact the corresponding authors to retrieve the missing information. If this was not possible, the reported outcome measure, clinical pregnancy or ongoing pregnancy was converted to live birth in 12 studies using published data (Arce et al., 2005). No significant difference was present in the probability of live birth between the two GnRH analogues [odds ratio (OR), 0.86; 95% confidence intervals (CI), 0.72 to 1.02]. This result remains stable in subgroup analysis that ordered the studies by type of population studied, gonadotrophin type used for stimulation, type of agonist protocol used, type of agonist used, type of antagonist protocol used, type of antagonist used, presence of allocation concealment, presence of co-intervention and the way the information on live birth was retrieved. In conclusion, the probability of live birth after ovarian stimulation for IVF does not depend on the type of analogue used for pituitary suppression.

Female↗

Addition of estradiol to progesterone for luteal supplementation in patients stimulated with GnRH antagonist/rFSH for IVF: a randomized controlled trial.

BACKGROUND: The role of progesterone for luteal support in stimulated cycles for IVF is well established. However, controversy still surrounds the benefit of additional supplementation with estradiol (E2) in GnRH agonist (GnRHa) cycles, while no such data are available for GnRH antagonists. The aim of this randomized controlled trial (RCT) was to compare ongoing pregnancy rates in patients stimulated with recombinant FSH (rFSH) and GnRH antagonist for IVF, who received micronized progesterone for luteal phase supplementation, with or without the addition of E2. METHODS: Two hundred and one patients underwent ovarian stimulation with a fixed dose of 200 IU rFSH and GnRH antagonist. Patients were randomized to receive, for luteal phase supplementation, either 600 mg of micronized progesterone vaginally (n=100, progesterone group) or 600 mg of micronized progesterone and 4 mg of E2 valerate orally (n=101, progesterone/E2 group). The main outcome measure was ongoing pregnancy at 12 weeks per patient randomized. RESULTS: Demographics, stimulation parameters and embryological data were comparable for the two groups compared. Twenty-six ongoing pregnancies were achieved in the progesterone (26%) and 30 in the progesterone/E2 group (29.7%). (Difference: 3.7 and 95%, CI: -15.8 to 8.6%). CONCLUSION: It appears that the addition of E2 to progesterone in the luteal phase after stimulation with rFSH and GnRH antagonist does not enhance the probability of pregnancy.

Chorionic Gonadotropin↗

GnRH antagonists in ovarian stimulation for IVF.

The present review describes, on the basis of the currently available evidence, the consensus reached by a group of experts on the use of gonadotropin-releasing hormone (GnRH) antagonists in ovarian stimulation for IVF. The single or multiple low-dose administration of GnRH antagonist during the late-follicular phase effectively prevents a premature rise in serum luteinizing hormone (LH) levels in most women. Although controversy remains, most comparative studies suggest a slight, not significant reduction in the probability of pregnancy after IVF using GnRH antagonist versus GnRH agonist co-treatment. Published meta-analyses suggest that this slight difference in pregnancy rates is not attributed to chance. Further studies applying varying treatment regimens and outcome measures are required. Data are not in favour of a need to modify the starting dose of gonadotropins. Data are not in favour of increasing gonadotropin dose at GnRH antagonist initiation. The addition of LH from the initiation of ovarian stimulation or from GnRH antagonist administration does not appear to be necessary. Replacement of human chorionic gonadotropin (HCG) by GnRH agonist for triggering final oocyte maturation is associated with a lower probability of pregnancy. The optimal timing for HCG administration needs to be explored further. GnRH antagonist initiation on day 6 of stimulation appears to be superior to flexible initiation by a follicle of 14-16 mm, although earlier GnRH antagonist administration is worth further evaluation. Luteal phase supplementation in GnRH antagonist protocols remains mandatory in IVF. Effects of GnRH antagonist co-treatment on the incidence of ovarian hyperstimulation syndrome remains uncertain, although a trend is present in favour of the GnRH antagonists. The role of GnRH antagonists in ovarian stimulation for IVF appears to be promising, although many questions regarding preferred dose regimens and effects on clinical outcomes remain.

Chorionic Gonadotropin↗

GnRH-antagonists in ovarian stimulation for IVF in patients with poor response to gonadotrophins, polycystic ovary syndrome, and risk of ovarian hyperstimulation: a meta-analysis.

This article is a systematic review of the literature on utilization of gonadotrophin-releasing hormone antagonists (GnRH-ant) for ovarian stimulation for IVF in special patient groups. Summarized by meta-analysis are the data from randomized controlled trials (RCT) in which GnRH-agonist (GnRH-a) and GnRH-ant were compared (eight RCT for poor response, four RCT for PCOS). Also reviewed are the data from two RCT and 13 retrospective or observational trials in which patients at risk of ovarian hyperstimulation syndrome (OHSS) were triggered with GnRH-agonist instead of HCG. For poor responders, no differences in clinical outcomes were found, except a significantly higher number of cumulus-oocyte complexes in GnRH-antagonist multiple dose protocol as compared to GnRH-agonist long protocol (P=0.05). For PCOS patients, no differences in outcomes were found, except a significantly shorter duration of stimulation, when GnRH-antagonist multiple dose protocol and GnRH-agonist long protocol are compared (P<0.01). However, sample sizes are still small and power to detect subtle differences is therefore limited. For OHSS risk patients triggered with GnRH-agonist, reports on the efficacy of this measure vary in the literature. GnRH-agonist triggering appears to be associated with a reduction in the incidence of mild and moderate OHSS. For prevention of severe OHSS, as yet, only very limited evidence is available.

Drug Administration Schedule↗

GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis.

Triggering final oocyte maturation with GnRH agonist during ovarian stimulation is feasible when inhibition of premature LH surge is performed with GnRH antagonists, and we aimed to systematically collate evidence on the clinical efficacy of GnRH agonist triggering in patients undergoing assisted reproduction in GnRH antagonist protocols. Twenty-three publications were identified by a comprehensive literature search that included PubMed, Embase and the Cochrane Library. Three publications out of 23 fulfilled the inclusion criteria for meta-analysis, which were (i) prospective, randomized controlled study design; (ii) stimulation with gonadotropins for induction of multifollicular development; (iii) suppression of endogenous LH by a GnRH antagonist; (iv) triggering of final oocyte maturation with GnRH agonist; (v) control group randomized to receive HCG for final oocyte maturation and (vi) any means of luteal phase support other than HCG. The participants were normoovulatory women undergoing IVF. The outcomes assessed were clinical pregnancy per randomized patient; number of oocytes retrieved; proportion of metaphase II oocytes; fertilization rate; embryo quality score; first trimester abortion rate; ovarian hyperstimulation syndrome (OHSS) incidence. Results are presented as combined standardized differences of the mean and combined odds ratios, as appropriate, with 95% confidence intervals. No significant difference was found for the number of oocytes retrieved (-0.94, -0.33-0.14), proportion of metaphase II oocytes (-0.03, -0.58-0.52), fertilization rate (0.15, -0.09-0.38) or embryo quality score (0.05, -0.18-0.29). No OHSS occurred in two of the studies, whereas in one study OHSS incidence was not reported. Thus from the available data, no conclusion can be drawn as regards OHSS incidence after GnRH agonist triggering. In comparison to HCG, GnRH agonist administration is associated with a significantly reduced likelihood of achieving a clinical pregnancy (0.21, 0.05-0.84; P = 0.03). The odds of first trimester pregnancy loss is increased after GnRH agonist triggering; however, the confidence interval crosses unity (11.51, 0.95-138.98; P = 0.05). In conclusion, the use of GnRH agonist to trigger final oocyte maturation in IVF, where inhibition of premature LH surge is achieved with GnRH antagonists, yields a number of oocytes capable to undergo fertilization and subsequent embryonic cleavage, which is comparable to that achieved with HCG. However, the likelihood of an ongoing clinical pregnancy after GnRH agonist triggering is significantly lower as compared to standard HCG treatment.

Abortion, Spontaneous↗

Are endogenous LH levels during ovarian stimulation for IVF using GnRH analogues associated with the probability of ongoing pregnancy? A systematic review.

The aim of this systematic review was to evaluate, among women with normal ovulation or World Health Organization (WHO) II oligoanovulation who undergo ovarian stimulation for IVF using GnRH analogues, whether endogenous LH levels predict the likelihood of ongoing pregnancy beyond 12 weeks. A literature search identified six studies that answered the research question, among which two were prospective studies (one in GnRH agonist and one in GnRH antagonist cycles). None of the retrospective studies suggest that low endogenous LH levels are associated with a significantly decreased probability of ongoing pregnancy beyond 12 weeks in such patients. In the two prospective studies high endogenous LH levels during down-regulation were associated with a decreased probability of ongoing pregnancy beyond 12 weeks. Until further prospective studies modify the existing evidence summarized here, an adverse effect of low endogenous LH levels on the probability of ongoing pregnancy beyond 12 weeks is not a sensible rationale for LH supplementation during ovarian stimulation for IVF using GnRH analogues.

Female↗

A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists.

BACKGROUND: Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH antagonists remains to be assessed. METHODS: 106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established. RESULTS: No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52). CONCLUSIONS: Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH antagonists.

Adult↗

Profound LH suppression after GnRH antagonist administration is associated with a significantly higher ongoing pregnancy rate in IVF.

BACKGROUND: The significance of suppressed LH levels in GnRH antagonist cycles for IVF outcome is currently unknown. The purpose of this study was to evaluate prospectively the association between LH levels and ongoing pregnancy achievement after GnRH antagonist initiation in IVF cycles. METHODS: Ovarian stimulation with a fixed dose of 200 IU recombinant FSH and daily GnRH antagonist (ganirelix) 0.25 mg from day 6 of stimulation was initiated in 116 women. Patients were not pretreated with an oral contraceptive. Induction of final oocyte maturation was performed with HCG 10,000 IU as soon as three follicles of > or =17 mm were present in ultrasound, and was followed by oocyte pick-up, conventional IVF or ICSI, and embryo transfer. The luteal phase was supplemented with vaginal progesterone. RESULTS: A significant decrease of both ongoing pregnancy rate and implantation rate was present across groups of patients with increasing LH levels. The highest implantation rate and ongoing pregnancy rate was present in those patients with LH levels on day 8 of stimulation < or =0.5 IU/l. CONCLUSIONS: Profound suppression of LH on day 8 of stimulation is associated with a significantly higher chance of achieving an ongoing pregnancy. More studies are necessary to evaluate this phenomenon further.

Adult↗

Should we advise patients undergoing IVF to start a cycle leading to a day 3 or a day 5 transfer?

BACKGROUND: The aim of this study was to compare ongoing pregnancy rates per started cycle between patients randomized at consultation to have embryo transfer either on day 3 or on day 5 of in-vitro culture. METHODS: All patients <43 years of age for whom IVF was indicated were allowed to participate in the study (day 3 group, 234 patients; day 5 group, 226 patients). Ovarian stimulation was performed either using GnRH antagonists/recombinant FSH (rFSH) (day 3, 70.1% of patients; day 5, 72.6% of patients) or using the long GnRH agonist protocol/urinary gonadotropins (day 3, 29.9% of patients; day 5 27.4% of patients). RESULTS: The random decision to initiate a cycle leading to day 5 as compared with a day 3 transfer was associated with a significantly lower chance of embryo cryopreservation (day 3, 61.5%; day 5, 50.4%; P<0.02). Ongoing pregnancy rate per started cycle did not differ between the two groups compared [day 3, 32.1%, 95% confidence interval (CI) 26.4-38.2%; day 5, 33.2%, 95% CI 27.3-39.5%]. CONCLUSIONS: Advising patients at consultation to initiate an IVF cycle leading to a day 5 as compared with a day 3 transfer does not appear to increase the probability of ongoing pregnancy, and is associated with a significantly lower probability of obtaining cryopreserved embryos.

Adult↗

Elevated progesterone at initiation of stimulation is associated with a lower ongoing pregnancy rate after IVF using GnRH antagonists.

BACKGROUND: The objective of this prospective study was to assess the impact of elevated serum progesterone levels on day 2 of the cycle on pregnancy rates in patients treated by IVF using GnRH antagonists. METHODS: Ovarian stimulation was started on day 2 of the cycle if progesterone levels were normal (normal-P group, n = 390). In the presence of elevated progesterone, initiation of stimulation was postponed for 1 or 2 days (high-P group, n = 20) and was started if repeat progesterone levels returned to normal range (n = 16). Stimulation was performed with recombinant FSH (rFSH) and GnRH antagonist was always started on day 6 of stimulation. RESULTS: A significantly higher exposure to progesterone and a significantly lower exposure to estradiol was present in the high-P as compared with the normal-P group from day 1 to day 8 of stimulation. In addition, a significantly lower ongoing pregnancy rate both per started cycle (5.0% versus 31.8%; P = 0.01) and per embryo transfer (6.3% versus 36.9%; P = 0.01) was present in the high-P compared with the normal-P group, respectively. CONCLUSIONS: The presence of elevated serum progesterone on day 2 of the cycle is associated with a decreased chance of pregnancy in patients treated with rFSH and GnRH antagonists.

Adult↗

Endometrial thickness cannot predict ongoing pregnancy achievement in cycles stimulated with clomiphene citrate for intrauterine insemination.

To date, limited data exist concerning the relation between endometrial thickness on the day of human chorionic gonadotrohin (HCG) administration and ongoing pregnancy achievement in cycles stimulated with clomiphene citrate for intrauterine insemination (IUI). In a prospective study, 168 couples were stimulated with clomiphene citrate from day 3 to day 7 of the cycle and endometrial thickness was assessed by ultrasound three times on the day of ovulation triggering. Ovulation was induced with HCG as soon as >/=1 follicle of >/=17 mm was present at ultrasound independently of endometrial thickness. IUI was performed 36 h after HCG administration. The main outcome measure was ongoing pregnancy. No difference was observed in endometrial thickness between patients who did or did not achieve an ongoing pregnancy (7.6 +/- 0.3 versus 7.6 +/- 0.2 respectively; P = 0.7). No discriminative ability of endometrial thickness on the achievement of ongoing pregnancy could be shown by receiver operating characteristic (ROC) curve analysis (area under the ROC curve 0.51, 95% CI: 0.44-0.59). In conclusion, endometrial thickness cannot predict ongoing pregnancy achievement in IUI cycles stimulated with clomiphene citrate.

Adult↗

[Optimizing ovarian stimulation for IVF using GnRH antagonists].

ART teams have failed to predict that pregnancy rates in GnRH antagonist regimens will be lower compared to the agonist regimens. No evidence appears to exist for an adverse effect of GnRH antagonists on oocyte/embryo quality. Abnormal development of endometrium at OPU is present in all cycles stimulated with GnRH antagonists and it is also encountered in all stimulation schemes using gonadotropins. Endometrium advancement is negatively associated with the probability of pregnancy. Endometrium histology at oocyte retrieval is positively associated with LH levels at initiation of stimulation and the duration of rec FSH stimulation prior to antagonist initiation. The presence of elevated serum progesterone on day two of the cycle is associated with a higher exposure to progesterone and a decreased probability of pregnancy. The higher the LH levels on day 8 of stimulation, the lower the probability of pregnancy. Low E2 levels on the day of hCG administration are not associated with a decreased probability of pregnancy. Ovarian stimulation for IVF alters steroid receptor kinetics in the follicular phase. Prolongation of follicular phase is associated with a decreased probability of pregnancy. Prolongation of follicular phase results in secretory changes of endometrium at OPU.

Anovulation↗

Implantation potential and clinical impact of cryopreservation--a review.

The ability of human embryos to survive the freezing and thawing process is reflected in their implantation potential. Although cryopreservation appears to affect adversely the capacity of human embryos to implant, it has also been shown to enhance consistently IVF outcome. Moreover, despite the reduced implantation potential of cryopreserved embryos as compared to fresh embryos, multiple pregnancies are frequent in frozen embryo transfer (FRET) cycles. There is no conclusive evidence that the stage of development at the time of freezing provides a clear advantage for the outcome of a FRET cycle. On the other hand, a decreased chance for pregnancy achievement appears to exist with advanced maternal age. Neither the mode of endometrium preparation nor the length of cryostorage appears to affect the outcome of FRET cycles which is positively associated to the achievement of pregnancy in the corresponding fresh cycle. Available evidence suggests that there are no adverse consequences in the babies born after embryo cryopreservation, although larger studies are necessary to allow solid conclusions.

Adult↗

Direct ovarian effects and safety aspects of GnRH agonists and antagonists.

The wide application of gonadotrophin-releasing hormone (GnRH) analogues in assisted reproduction has raised concerns about their potential extra-pituitary actions. Although data from animal studies support the presence of ovarian GnRH receptors and of direct ovarian effects of GnRH analogues, this has not been unequivocally demonstrated in humans. Available evidence suggests, however, the existence of GnRH receptors in human granulosa-luteal cells, while the majority of the studies performed showed that progesterone is inhibited by GnRH agonists in vitro. On the other hand, no difference seems to exist between agonists and antagonists in terms of granulosa-luteal cell steroidogenesis under basal conditions. So far, no studies have suggested an adverse effect of GnRH analogues on the developing human follicle. Moreover, the physiological significance of a direct in-vitro ovarian effect of GnRH analogues remains to be established.

Amino Acid Sequence↗

Evaluation of intrauterine insemination with washed spermatozoa from the husband in the treatment of infertility.

In this study, we examined the efficacy of intrauterine insemination with washed spermatozoa from the husband (AIH/IUI) in the treatment of infertility. A total of 127 treatment cycles were completed (1.95 cycles per patient). The indications for AIH/IUI were male subfertility (group I: 53 couples), cervical factor (group II: four couples), male and cervical factor (group III: six couples) and unexplained infertility (group IV: two couples). Sperm washing caused a reduction of the sperm concentration from 52 x 10(6)/ml to 44 x 10(6)/ml (P less than 0.08) and motility from 49% to 45% (P less than 0.03). Twelve pregnancies were achieved (18.5% per couple and 9.5% per cycle): eight pregnancies in group I (15.1%), one in group II (25%) and three in group III (50%). Of the 12 pregnancies, eight occurred in the first insemination cycle, three in the second and one in the third (1.4 cycles/pregnancy). Sperm motility was significantly higher in the pregnant than in the non-pregnant group (65.5% versus 46.4%, respectively; P less than 0.004), whereas no significant difference was observed in the sperm concentration between these two groups (39 x 10(6)/ml and 54 x 10(6)/ml, respectively). In conclusion, AIH/IUI is a technically easy and non-invasive procedure which offers a satisfactory pregnancy rate in selected couples with male subfertility and/or cervical factor infertility.

Adult↗

Evaluation of Hamilton-Thorn automated semen analysis system.

Sperm concentration and percentage motility values generated by the HT M-2030 system (CASA) were compared with those obtained by subjective semen analysis (SSA). Three calibrations arbitrarily designated as A, M, and D for gates and discriminators and three calibrations arbitrarily designated LI, MI, and HI for default pixel count (DPC) and default intensity (DI) were evaluated. The best correlation between CASA and SSA was observed utilizing M calibration (n = 114) with which sperm concentration was +0.3 x 10(6)/mL (r = .96) and motility was -6.3% (r = .89) compared to the values obtained by SSA. It was found that 35.9% of sperm concentration values and 34.2% of sperm motility values were within 10% of the values obtained by SSA. When sperm concentration was between 50 and 100 x 10(6)/mL the difference in motility was reduced (-3.2%) while the difference in sperm concentration was reversed (-2.6 x 10(6)/mL). LI calibration (DPC = 4, DI = 86) gave acceptable results with M calibration for sperm concentration (+2.1 x 10(6)/mL) and motility (-6.9%) compared to the values obtained by SSA. In the presence of sperm clumping, the difference between CASA and SSA was reversed for sperm concentration (+0.56 x 10(6)/mL for normal samples vs. -2.2 x 10(6)/mL for samples with clumping) and was reduced for sperm motility (-7.14% vs. -4.55%, respectively). HT M-2030 under proper calibration can be used as a rapid, objective, and reliable alternative to conventional semen analysis in routine and for research purposes.

Calibration↗

Effect of follicular fluid on the kinetics of human sperm acrosome reaction in vitro.

The purpose of the present study was to evaluate the kinetics of human sperm acrosome reaction in vitro using the triple stain technique. Acrosome reaction was studied in sperm samples from 16 fertile men 2, 6, and 9 h after ejaculation, following incubation in culture medium (CM; Ham's F-10), with a mixture of CM and follicular fluid (FF), or with FF only. Incubation of sperm samples without the influence of any medium served as control. The highest proportion of living acrosome-reacted sperm after a 2-h incubation period occurred in samples incubated with FF (18%), followed by samples incubated with the mixture (15.2%), and then with CM (11.8%). The proportion of living sperm that had undergone the acrosome reaction in the control group was significantly lower (5.7%, p < 0.05). After 6 h of incubation, live acrosome-reacted sperm in FF had increased to 39%, in the mixture to 35.5%, and in CM to 30.5%, whereas in the control group the increase was only 6.3% (p < 0.05). After 9 h of incubation, the percentage of living reacted sperm showed a decline compared with the percentage at 6 h. This decline was greater in samples incubated with FF (from 39 to 19.8%) than in samples incubated with the mixture (from 35.5 to 23.6%). Samples incubated in CM only showed a small decrease from 30.5 to 28.4%, while in the control group this percentage decreased from 6.3 to 2.3%. In conclusion, incubation of sperm in suitable media favorably influences the acrosome reaction, inducing an increase in the percentage of live acrosome-reacted sperm.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗