E. Kolibianakis | AUTH - Academia.edu (original) (raw)

Papers by E. Kolibianakis

Human Reproduction, 2004

BACKGROUND: The significance of suppressed LH levels in GnRH antagonist cycles for IVF outcome is... more 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 $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 #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.

Reproductive BioMedicine Online, 2005

The present review summarizes existing knowledge on the use of gonadotropin releasing hormone (Gn... more 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.

Current Opinion in Obstetrics and Gynecology, 2009

To summarize the available evidence from randomized controlled trials comparing vitrification ver... more To summarize the available evidence from randomized controlled trials comparing vitrification versus slow freezing for cryopreservation of human embryos. Vitrification, as compared with slow freezing, appears to be better in terms of postthawing survival rates both for cleavage-stage embryos [odds ratio (OR): 6.35, 95% confidence interval (CI): 1.14-35.26, random effects model] and for blastocysts (OR: 4.09, 95% CI: 2.45-6.84, random effects model). Furthermore, postthawing blastocyst development of embryos cryopreserved in the cleavage stage is significantly higher with vitrification as compared with slow freezing (OR: 1.56, 95% CI: 1.07-2.27, fixed effects model). No significant difference in clinical pregnancy rates per transfer could be detected between the two cryopreservation methods (OR: 1.66, 95% CI: 0.98-2.79). Currently, vitrification does not appear to be associated with an increased probability of pregnancy. However, a significant advantage of vitrification over slow freezing in terms of postthawing survival rates is present for embryos cryopreserved both at the cleavage and at the blastocyst stages. The above conclusions are based on limited data, and thus further properly designed randomized controlled trials are needed.

The purpose of this prospective study was to assess the reproductive outcome of patients with pol... more The purpose of this prospective study was to assess the reproductive outcome of patients with polycystic ovarian syndrome (PCOS) treated by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with recombinant FSH (rFSH) and gonadotrophin releasing hormone (GnRH) antagonists. One hundred and ten patients were evaluated. The starting dose of rFSH was 100 IU in 67 women with body mass index (BMI) </=29 kg/m(2) and 200 IU in 43 women with BMI >29 kg/m(2). GnRH antagonist was started by the detection of a follicle of a 15mm in ultrasound scan. A significantly lower ongoing pregnancy rate per oocyte retrieval (25.6% versus 46.7%, P = 0.04) and a higher occurrence of ovarian hyperstimulation syndrome (16.3% versus 3.0%, P = 0.03) was observed in the group of patients with BMI >29 kg/m(2) as compared with the group of patients with BMI </=29 kg/m(2), respectively. In conclusion, in GnRH antagonist cycles a worse reproductive outcome is expected in PCOS patients with BMI >29 kg/m(2) in whom stimulation is initiated with 200 IU of rFSH as compared with PCOS patients with BMI </=29 kg/m(2) in whom stimulation is initiated with 100 IU of rFSH.

The purpose of this pilot study was to compare the endocrinological environment of cycles stimula... more The purpose of this pilot study was to compare the endocrinological environment of cycles stimulated with clomiphene citrate (CC) or letrozole. Fifteen patients undergoing intrauterine insemination (IUI) received from day 3 to day 7 of the cycle either letrozole 2.5 mg/day (n = 7) or clomiphene citrate 100 mg/day (n = 8). IUI was performed one day after the detection of LH peak. No luteal support was administered. Significantly lower serum oestradiol concentrations were present in the follicular phase on days 9, 13 and 15 of the cycle and in the luteal phase on days 3 and 6 post-IUI in the letrozole group compared with those in the CC group. Progesterone concentrations and oestradiol concentrations were significantly lower in the letrozole group than in the CC group on the day of LH peak. Significantly more follicles developed in patients in the CC group compared with those in the letrozole group. In conclusion, significantly lower oestradiol concentrations and fewer follicles are observed in cycles stimulated with 2.5 mg letrozole compared with cycles stimulated with 100 mg CC from day 3 to day 7 of the cycle.

Human Reproduction, 2014

Does substituting 150 µg corifollitropin alfa for 450 IU follitropin beta during the first 7 days... more Does substituting 150 µg corifollitropin alfa for 450 IU follitropin beta during the first 7 days of ovarian stimulation in proven poor responders, result in retrieval of a non-inferior number (<1.5 fewer) of cumulus oocyte complexes (COCs)? A single s.c. dose of 150 µg corifollitropin alfa on the first day of ovarian stimulation, followed if necessary, from Day 8 onwards, with 450 IU of follitropin beta/day, is not inferior to daily doses of 450 IU follitropin beta. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1 within the safety margin of 1.5. Recent data from retrospective studies suggest that the use of corifollitropin alfa in poor responders is promising since it could simplify ovarian stimulation without compromising its outcome. Seventy-nine women with previous poor ovarian response undergoing ICSI treatment were enrolled in this open label, non-inferiority, randomized clinical trial (RCT). Inclusion criteria were: previous poor response to ovarian stimulation (≤4 COCs) after maximal stimulation, age <45 years, regular spontaneous menstrual cycle, body mass index: 18-32 kg/m(2) and basal follicle stimulating hormone ≤20 IU/l. On Day 2 of the menstrual cycle, patients were administered either a single s.c dose of 150 µg corifollitropin alfa (n = 40) or a fixed daily dose of 450 IU of follitropin beta (n = 39). In the corifollitropin alfa group, 450 IU of follitropin beta were administered from Day 8 of stimulation until the day of human chorionic gonadotrophin (hCG) administration, if necessary. To inhibit premature luteinizing hormone surge, the gonadotrophin releasing hormone antagonist ganirelix was used. Triggering of final oocyte maturation was performed using 250 µg of recombinant hCG, when at least two follicles reached 17 mm in mean diameter. The number of COCs retrieved was not statistically different between the corifollitropin alfa and the follitropin beta groups [Median 3 versus 2, 95% CI 2-4, 2-3, respectively, P = 0.26]. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1. A multivariable analysis adjusting for all the potential baseline differences confirmed this finding. No significant difference was observed regarding the probability of live birth between the corifollitropin alfa and the follitropin beta group (live birth per patient reaching oocyte retrieval: 7.9 versus 2.6%, respectively, difference +5.3%, 95% CI: -6.8 to +18.3). The present study was not powered to test a smaller difference (e.g. 1 COC) in terms of COCs retrieved as well as to show potential differences in the probability of pregnancy. Moreover, it would be interesting to assess whether the continuation of stimulation in the long acting FSH arm, where necessary, with 200 IU instead of 450 IU of follitropin beta would have altered the direction or the magnitude of the effect of the type of FSH, observed on the number of COCs retrieved. Corifollitropin alfa simplifies IVF treatment because it is administered in a GnRH antagonist protocol and replaces seven daily FSH injections with a single one of a long acting FSH without compromising the outcome. It could greatly reduce the burden of treatment for poor responders and this deserves further investigation. No external funding was used for this study. None of the authors has any conflict of interest to declare. NCT02046655.

Ovarian Stimulation, 2010

Reproductive BioMedicine Online, 2013

International Journal of Gynecology & Obstetrics, 2000

Human Reproduction, 2004

A 36-year-old single woman presented at the out-patient clinic in March 2000 requesting donor ins... more A 36-year-old single woman presented at the out-patient clinic in March 2000 requesting donor insemination. Between May 2000 and May 2001 she underwent six cycles of intrauterine insemination with donor sperm after clomiphene citrate stimulation without achieving a pregnancy. In January 2002, ICSI was performed; two embryos were transferred on day 3 and a dizygotic bichorionic pregnancy was achieved, which ended in a miscarriage at 21 weeks of gestation. After a second unsuccessful ICSI attempt in which a single embryo transfer was performed, she embarked upon her third attempt in March 2003 at 39 years of age. Two blastocysts were transferred after ICSI, resulting in a quintuplet gestation consisting of a monochorionic biamniotic pregnancy and a monochorionic triamniotic pregnancy. The current case report indicates that monozygotic pregnancies consisting of both twins and triplets are possible after treatment by assisted reproductive technologies. An association between extended culture, manipulation of the zona pellucida, ovarian stimulation and occurrence of monozygotic pregnancies has been suggested by retrospective studies. However, in order to identify more reliably predictive factors for the occurrence of monozygotic pregnancies, it is necessary to perform prospective trials.

Human Reproduction, 2004

The purpose of this study was to evaluate the use of the modified natural cycle (MNC) for IVF in ... more The purpose of this study was to evaluate the use of the modified natural cycle (MNC) for IVF in poor responders as a last resort prior to oocyte donation. Thirty-two patients with a regular menstrual cycle, FSH levels on day 3 of the cycle >12 IU/l and one or more failed IVF cycles with five or fewer cumulus-oocyte complexes (COCs) retrieved were included in this prospective study. Recombinant FSH 100 IU and GnRH antagonist 0.25 mg/day were started concomitantly when a follicle with a mean diameter of 14 mm was present at ultrasound. HCG 10 000 IU was administered as soon as the mean follicular diameter was > or =16 mm. Twenty-five out of 78 cycles performed (32.1%) did not result in oocyte retrieval. In nine out of 53 cycles (16.9%) in which oocyte retrieval was performed, no COCs were retrieved. Following fertilization, embryo transfer was performed in 19 out of 44 cycles in which COCs were retrieved (43.2%). No ongoing pregnancy was achieved in 78 MNCs (0.0%; 95% confidence interval 0.0-4.7). MNC does not offer a realistic chance of parenthood in patients with high levels of FSH on day 3 of the cycle and previous poor response to ovarian stimulation, when offered as a last resort prior to oocyte donation.

Fertility and Sterility, 2004

Fertility and Sterility, 2007

Both cleavage-stage and blastocyst-stage embryo transfer policies have advantages and drawbacks. ... more Both cleavage-stage and blastocyst-stage embryo transfer policies have advantages and drawbacks. The number of embryos transferred, however, is a crucial parameter that needs to be considered before attempting any comparison. An extensive literature search yielded initially 282 studies from which 8 randomized controlled trials met the inclusion criteria: (i) truly randomized design (ii) policy to transfer equal number of embryos in both the cleavage-stage and the blastocyst-stage groups and (iii) published as full text in a peer-review journal. Primary outcome was the live birth rate and secondary outcomes were clinical pregnancy rate, multiple pregnancy rate, cancellation rate and cryopreservation rate. A total of 1654 patients were reviewed. Live birth rate per randomized patient was significantly higher (n = 6 studies) in patients who had a blastocyst-stage transfer as compared to patients with cleavage-stage embryo transfer [odds ratio (OR): 1.39, 95% confidence interval (CI): 1.10-1.76; P = 0.005]. Clinical pregnancy rate (OR: 1.27, 95% CI: 1.03-1.55; P = 0.02) and cancellation rate per patient randomized (OR: 2.21, 95% CI: 1.47-3.32; P = 0.0001) were significantly higher in patients with a blastocyst-stage embryo transfer as compared to patients in whom a cleavage-stage embryo transfer was performed. The cryopreservation rate was significantly higher in the cleavage-stage group (OR: 0.28, 95% CI: 0.14-0.55; P = 0.0002). The best available evidence suggests that the probability of live birth after fresh IVF is significantly higher after blastocyst-stage embryo transfer as compared to cleavage-stage embryo transfer when equal number of embryos are transferred in the two groups compared.

Fertility and Sterility, 2007

To report the outcome of frozen-thawed embryo replacement cycles after GnRH-agonist triggering of... more To report the outcome of frozen-thawed embryo replacement cycles after GnRH-agonist triggering of final oocyte maturation in the collecting cycle with GnRH-antagonist. Prospective, observational, multicentric clinical study. Tertiary university-affiliated IVF centers. Patients under observation previously had been recruited into two concurrently performed, independent, randomized controlled trials (comparing hCG with GnRH-agonist for triggering final oocyte maturation in GnRH-antagonist multiple-dose protocols in normal responder patients) encompassing a total of 228 participants. Surplus embryos or oocytes at the pronuclear stage were cryopreserved in 53 patients after hCG administration and 32 patients after GnRH-agonist administration on the basis of patient choice, pronuclear/embryo availability, and local laws. Transfer of frozen-thawed embryos. Live birth rate. Thirty-one and 23 patients after administration of hCG and GnRH-agonist, respectively, started a frozen-embryo replacement cycle by September 2005, with 25 and 16 patients eventually undergoing at least one frozen-thawed ET. Live birth rate per ET was 18.5% (95% confidence interval [CI], 8.2-36.7) and 30.0% (95% CI, 14.5-51.9) after hCG and GnRH-agonist triggering, respectively. Cumulative live birth rate per patient starting a frozen-embryo replacement cycle was 16.1% (95% CI, 7.1-32.6) and 26.1% (95% CI, 12.5-46.5) for hCG and GnRH-agonist, respectively. The likelihood of live birth in frozen-embryo replacement cycles after GnRH-agonist triggering of final oocyte maturation does not appear to be impaired.

Human Reproduction, 2004

BACKGROUND: The significance of suppressed LH levels in GnRH antagonist cycles for IVF outcome is... more 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 $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 #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.

Reproductive BioMedicine Online, 2005

The present review summarizes existing knowledge on the use of gonadotropin releasing hormone (Gn... more 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.

Current Opinion in Obstetrics and Gynecology, 2009

To summarize the available evidence from randomized controlled trials comparing vitrification ver... more To summarize the available evidence from randomized controlled trials comparing vitrification versus slow freezing for cryopreservation of human embryos. Vitrification, as compared with slow freezing, appears to be better in terms of postthawing survival rates both for cleavage-stage embryos [odds ratio (OR): 6.35, 95% confidence interval (CI): 1.14-35.26, random effects model] and for blastocysts (OR: 4.09, 95% CI: 2.45-6.84, random effects model). Furthermore, postthawing blastocyst development of embryos cryopreserved in the cleavage stage is significantly higher with vitrification as compared with slow freezing (OR: 1.56, 95% CI: 1.07-2.27, fixed effects model). No significant difference in clinical pregnancy rates per transfer could be detected between the two cryopreservation methods (OR: 1.66, 95% CI: 0.98-2.79). Currently, vitrification does not appear to be associated with an increased probability of pregnancy. However, a significant advantage of vitrification over slow freezing in terms of postthawing survival rates is present for embryos cryopreserved both at the cleavage and at the blastocyst stages. The above conclusions are based on limited data, and thus further properly designed randomized controlled trials are needed.

The purpose of this prospective study was to assess the reproductive outcome of patients with pol... more The purpose of this prospective study was to assess the reproductive outcome of patients with polycystic ovarian syndrome (PCOS) treated by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with recombinant FSH (rFSH) and gonadotrophin releasing hormone (GnRH) antagonists. One hundred and ten patients were evaluated. The starting dose of rFSH was 100 IU in 67 women with body mass index (BMI) </=29 kg/m(2) and 200 IU in 43 women with BMI >29 kg/m(2). GnRH antagonist was started by the detection of a follicle of a 15mm in ultrasound scan. A significantly lower ongoing pregnancy rate per oocyte retrieval (25.6% versus 46.7%, P = 0.04) and a higher occurrence of ovarian hyperstimulation syndrome (16.3% versus 3.0%, P = 0.03) was observed in the group of patients with BMI >29 kg/m(2) as compared with the group of patients with BMI </=29 kg/m(2), respectively. In conclusion, in GnRH antagonist cycles a worse reproductive outcome is expected in PCOS patients with BMI >29 kg/m(2) in whom stimulation is initiated with 200 IU of rFSH as compared with PCOS patients with BMI </=29 kg/m(2) in whom stimulation is initiated with 100 IU of rFSH.

The purpose of this pilot study was to compare the endocrinological environment of cycles stimula... more The purpose of this pilot study was to compare the endocrinological environment of cycles stimulated with clomiphene citrate (CC) or letrozole. Fifteen patients undergoing intrauterine insemination (IUI) received from day 3 to day 7 of the cycle either letrozole 2.5 mg/day (n = 7) or clomiphene citrate 100 mg/day (n = 8). IUI was performed one day after the detection of LH peak. No luteal support was administered. Significantly lower serum oestradiol concentrations were present in the follicular phase on days 9, 13 and 15 of the cycle and in the luteal phase on days 3 and 6 post-IUI in the letrozole group compared with those in the CC group. Progesterone concentrations and oestradiol concentrations were significantly lower in the letrozole group than in the CC group on the day of LH peak. Significantly more follicles developed in patients in the CC group compared with those in the letrozole group. In conclusion, significantly lower oestradiol concentrations and fewer follicles are observed in cycles stimulated with 2.5 mg letrozole compared with cycles stimulated with 100 mg CC from day 3 to day 7 of the cycle.

Human Reproduction, 2014

Does substituting 150 µg corifollitropin alfa for 450 IU follitropin beta during the first 7 days... more Does substituting 150 µg corifollitropin alfa for 450 IU follitropin beta during the first 7 days of ovarian stimulation in proven poor responders, result in retrieval of a non-inferior number (<1.5 fewer) of cumulus oocyte complexes (COCs)? A single s.c. dose of 150 µg corifollitropin alfa on the first day of ovarian stimulation, followed if necessary, from Day 8 onwards, with 450 IU of follitropin beta/day, is not inferior to daily doses of 450 IU follitropin beta. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1 within the safety margin of 1.5. Recent data from retrospective studies suggest that the use of corifollitropin alfa in poor responders is promising since it could simplify ovarian stimulation without compromising its outcome. Seventy-nine women with previous poor ovarian response undergoing ICSI treatment were enrolled in this open label, non-inferiority, randomized clinical trial (RCT). Inclusion criteria were: previous poor response to ovarian stimulation (≤4 COCs) after maximal stimulation, age <45 years, regular spontaneous menstrual cycle, body mass index: 18-32 kg/m(2) and basal follicle stimulating hormone ≤20 IU/l. On Day 2 of the menstrual cycle, patients were administered either a single s.c dose of 150 µg corifollitropin alfa (n = 40) or a fixed daily dose of 450 IU of follitropin beta (n = 39). In the corifollitropin alfa group, 450 IU of follitropin beta were administered from Day 8 of stimulation until the day of human chorionic gonadotrophin (hCG) administration, if necessary. To inhibit premature luteinizing hormone surge, the gonadotrophin releasing hormone antagonist ganirelix was used. Triggering of final oocyte maturation was performed using 250 µg of recombinant hCG, when at least two follicles reached 17 mm in mean diameter. The number of COCs retrieved was not statistically different between the corifollitropin alfa and the follitropin beta groups [Median 3 versus 2, 95% CI 2-4, 2-3, respectively, P = 0.26]. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1. A multivariable analysis adjusting for all the potential baseline differences confirmed this finding. No significant difference was observed regarding the probability of live birth between the corifollitropin alfa and the follitropin beta group (live birth per patient reaching oocyte retrieval: 7.9 versus 2.6%, respectively, difference +5.3%, 95% CI: -6.8 to +18.3). The present study was not powered to test a smaller difference (e.g. 1 COC) in terms of COCs retrieved as well as to show potential differences in the probability of pregnancy. Moreover, it would be interesting to assess whether the continuation of stimulation in the long acting FSH arm, where necessary, with 200 IU instead of 450 IU of follitropin beta would have altered the direction or the magnitude of the effect of the type of FSH, observed on the number of COCs retrieved. Corifollitropin alfa simplifies IVF treatment because it is administered in a GnRH antagonist protocol and replaces seven daily FSH injections with a single one of a long acting FSH without compromising the outcome. It could greatly reduce the burden of treatment for poor responders and this deserves further investigation. No external funding was used for this study. None of the authors has any conflict of interest to declare. NCT02046655.

Ovarian Stimulation, 2010

Reproductive BioMedicine Online, 2013

International Journal of Gynecology & Obstetrics, 2000

Human Reproduction, 2004

A 36-year-old single woman presented at the out-patient clinic in March 2000 requesting donor ins... more A 36-year-old single woman presented at the out-patient clinic in March 2000 requesting donor insemination. Between May 2000 and May 2001 she underwent six cycles of intrauterine insemination with donor sperm after clomiphene citrate stimulation without achieving a pregnancy. In January 2002, ICSI was performed; two embryos were transferred on day 3 and a dizygotic bichorionic pregnancy was achieved, which ended in a miscarriage at 21 weeks of gestation. After a second unsuccessful ICSI attempt in which a single embryo transfer was performed, she embarked upon her third attempt in March 2003 at 39 years of age. Two blastocysts were transferred after ICSI, resulting in a quintuplet gestation consisting of a monochorionic biamniotic pregnancy and a monochorionic triamniotic pregnancy. The current case report indicates that monozygotic pregnancies consisting of both twins and triplets are possible after treatment by assisted reproductive technologies. An association between extended culture, manipulation of the zona pellucida, ovarian stimulation and occurrence of monozygotic pregnancies has been suggested by retrospective studies. However, in order to identify more reliably predictive factors for the occurrence of monozygotic pregnancies, it is necessary to perform prospective trials.

Human Reproduction, 2004

The purpose of this study was to evaluate the use of the modified natural cycle (MNC) for IVF in ... more The purpose of this study was to evaluate the use of the modified natural cycle (MNC) for IVF in poor responders as a last resort prior to oocyte donation. Thirty-two patients with a regular menstrual cycle, FSH levels on day 3 of the cycle >12 IU/l and one or more failed IVF cycles with five or fewer cumulus-oocyte complexes (COCs) retrieved were included in this prospective study. Recombinant FSH 100 IU and GnRH antagonist 0.25 mg/day were started concomitantly when a follicle with a mean diameter of 14 mm was present at ultrasound. HCG 10 000 IU was administered as soon as the mean follicular diameter was > or =16 mm. Twenty-five out of 78 cycles performed (32.1%) did not result in oocyte retrieval. In nine out of 53 cycles (16.9%) in which oocyte retrieval was performed, no COCs were retrieved. Following fertilization, embryo transfer was performed in 19 out of 44 cycles in which COCs were retrieved (43.2%). No ongoing pregnancy was achieved in 78 MNCs (0.0%; 95% confidence interval 0.0-4.7). MNC does not offer a realistic chance of parenthood in patients with high levels of FSH on day 3 of the cycle and previous poor response to ovarian stimulation, when offered as a last resort prior to oocyte donation.

Fertility and Sterility, 2004

Fertility and Sterility, 2007

Both cleavage-stage and blastocyst-stage embryo transfer policies have advantages and drawbacks. ... more Both cleavage-stage and blastocyst-stage embryo transfer policies have advantages and drawbacks. The number of embryos transferred, however, is a crucial parameter that needs to be considered before attempting any comparison. An extensive literature search yielded initially 282 studies from which 8 randomized controlled trials met the inclusion criteria: (i) truly randomized design (ii) policy to transfer equal number of embryos in both the cleavage-stage and the blastocyst-stage groups and (iii) published as full text in a peer-review journal. Primary outcome was the live birth rate and secondary outcomes were clinical pregnancy rate, multiple pregnancy rate, cancellation rate and cryopreservation rate. A total of 1654 patients were reviewed. Live birth rate per randomized patient was significantly higher (n = 6 studies) in patients who had a blastocyst-stage transfer as compared to patients with cleavage-stage embryo transfer [odds ratio (OR): 1.39, 95% confidence interval (CI): 1.10-1.76; P = 0.005]. Clinical pregnancy rate (OR: 1.27, 95% CI: 1.03-1.55; P = 0.02) and cancellation rate per patient randomized (OR: 2.21, 95% CI: 1.47-3.32; P = 0.0001) were significantly higher in patients with a blastocyst-stage embryo transfer as compared to patients in whom a cleavage-stage embryo transfer was performed. The cryopreservation rate was significantly higher in the cleavage-stage group (OR: 0.28, 95% CI: 0.14-0.55; P = 0.0002). The best available evidence suggests that the probability of live birth after fresh IVF is significantly higher after blastocyst-stage embryo transfer as compared to cleavage-stage embryo transfer when equal number of embryos are transferred in the two groups compared.

Fertility and Sterility, 2007

To report the outcome of frozen-thawed embryo replacement cycles after GnRH-agonist triggering of... more To report the outcome of frozen-thawed embryo replacement cycles after GnRH-agonist triggering of final oocyte maturation in the collecting cycle with GnRH-antagonist. Prospective, observational, multicentric clinical study. Tertiary university-affiliated IVF centers. Patients under observation previously had been recruited into two concurrently performed, independent, randomized controlled trials (comparing hCG with GnRH-agonist for triggering final oocyte maturation in GnRH-antagonist multiple-dose protocols in normal responder patients) encompassing a total of 228 participants. Surplus embryos or oocytes at the pronuclear stage were cryopreserved in 53 patients after hCG administration and 32 patients after GnRH-agonist administration on the basis of patient choice, pronuclear/embryo availability, and local laws. Transfer of frozen-thawed embryos. Live birth rate. Thirty-one and 23 patients after administration of hCG and GnRH-agonist, respectively, started a frozen-embryo replacement cycle by September 2005, with 25 and 16 patients eventually undergoing at least one frozen-thawed ET. Live birth rate per ET was 18.5% (95% confidence interval [CI], 8.2-36.7) and 30.0% (95% CI, 14.5-51.9) after hCG and GnRH-agonist triggering, respectively. Cumulative live birth rate per patient starting a frozen-embryo replacement cycle was 16.1% (95% CI, 7.1-32.6) and 26.1% (95% CI, 12.5-46.5) for hCG and GnRH-agonist, respectively. The likelihood of live birth in frozen-embryo replacement cycles after GnRH-agonist triggering of final oocyte maturation does not appear to be impaired.