Daniel Bodri

Triggering with human chorionic gonadotropin or a gonadotropin-releasing hormone agonist in gonadotropin-releasing hormone antagonist-treated oocyte donor cycles : findings of a large retrospective cohort study

OBJECTIVE To compare pregnancy rates and the incidence of ovarian hyperstimulation syndrome (OHSS) in donor stimulation cycles where final maturation of oocytes was induced with recombinant hCG or GnRH agonist. DESIGN Retrospective, cohort study. SETTING Private infertility clinic. PATIENT(S) A total of 1171 egg donors performing 2077 stimulation cycles. INTERVENTION(S) Controlled ovarian hyperstimulation of egg donors with GnRH antagonist protocol triggered with recombinant hCG (rhCG; 250 microg) or GnRH agonist (triptorelin 0.2 mg) based on the physicians decision. MAIN OUTCOME MEASURE(S) Proportion of mature and fertilized oocytes per donor cycle; clinical, ongoing pregnancy and implantation rate in recipients; and incidence of moderate/severe OHSS in oocyte donors. RESULT(S) The proportion of mature oocytes was comparable, whereas the difference in the fertilization rate reached statistical significance (65% vs. 69%). No significant differences were observed in the implantation rate or clinical and ongoing pregnancy rates per ET. The incidence of moderate/severe OHSS was 1.26% (13/1031; 95% confidence interval [CI], 0.74-2.15) and 0% (0/1046; 95% CI, 0.00-0.37) in the rhCG and GnRH agonist groups, respectively. CONCLUSION(S) Recipient outcome was not significantly different when using oocytes from GnRH antagonist-treated donor cycles triggered with hCG or GnRH agonist. However, GnRH agonist triggering was associated with a lower incidence of moderate/severe OHSS in egg donors.

Complications related to ovarian stimulation and oocyte retrieval in 4052 oocyte donor cycles

A retrospective study was conducted in a private infertility centre to evaluate the rate of complications in a large oocyte donation programme. A total of 4052 oocyte retrievals were performed between January 2001 and October 2007. Altogether, 1238 cycles (30.6%) were stimulated with the use of gonadotrophin-releasing hormone (GnRH) agonists and in 2814 cycles (69.4%) the GnRH antagonist protocol was used. The GnRH antagonist treated cycles were triggered with human chorionic gonadotrophin (HCG) or a GnRH agonist in 1295 and 1519 cycles, respectively. Complications related to oocyte retrieval occurred in 17 patients (0.42%) (intra-abdominal bleeding: n = 14, severe pain: n = 2, ovarian torsion: n = 1). Fourteen of these were hospitalized (0.35%) and six donors (0.15%) required surgical intervention. Pelvic infections, injury to pelvic structures or anaesthesiological complications were not observed in this series. Moderate/severe ovarian hyperstimulation syndrome (OHSS) occurred in 22 donors; 11 required hospital admission and 11 were managed on an outpatient basis. All cases were related to HCG triggering (0.87%). Serious complications related to oocyte retrieval occurred at a low rate in healthy young donors. The risk of OHSS can be substantially reduced by specific stimulation protocols, which include GnRH agonist triggering. Prospective oocyte donors should be adequately counselled about the risks related to egg donation.

Neonatal outcome and birth defects in 6623 singletons born following minimal ovarian stimulation and vitrified versus fresh single embryo transfer

OBJECTIVE To compare neonatal outcome between children born after vitrified versus fresh single-embryo transfer (SET). STUDY DESIGN Retrospective, single-centre cohort study of 6623 delivered singletons following 29,944 single-embryo transfers. Patients underwent minimal ovarian stimulation/natural cycle IVF followed by SET of fresh or vitrified-warmed (using Cryotop, Kitazato) cleavage-stage embryos or blastocysts. Outcome measures were gestational age at delivery, birth weight, birth length, low birth weight (LBW), small for gestational age (SGA) and large for gestational age (LGA) infants, perinatal mortality and minor/major birth defects (evaluated by parent questionnaire). RESULTS Gestational age (38.6 ± 2 versus 38.7 ± 1.9 weeks) and preterm delivery rate (6.9% versus 6.9%, aOR: 0.96 95%CI: 0.76-1.22) in singletons born after the transfer of vitrified embryos were comparable to those born after the transfer of fresh embryos. Children born after the transfer of vitrified embryos had a higher birth weight (3028 ± 465 versus 2943 ± 470 g, p<0.0001) and lower LBW (8.5% versus 11.9%, aOR: 0.65 95%CI: 0.53-0.79) and SGA (3.6% versus 7.6% aOR: 0.43 95%CI: 0.33-0.56) rates. Total birth defect rates (including minor anomalies) (2.4% versus 1.9%, aOR: 1.41 95%CI: 0.96-2.10) and perinatal mortality rates (0.6% versus 0.5%, aOR: 1.02 95%CI: 0.21-4.85) were comparable between the vitrified and fresh groups. CONCLUSIONS Vitrification of embryos/blastocysts did not increase the incidence of adverse neonatal outcomes or birth defects following single embryo transfer.

Minimal ovarian stimulation combined with elective single embryo transfer policy: age-specific results of a large, single-centre, Japanese cohort

BackgroundThe two main complications associated with the use of assisted reproduction techniques, ovarian hyperstimulation syndrome and multiple pregnancies, could be eliminated by milder ovarian stimulation protocols and the increased use of a single embryo transfer (SET) policy. A retrospective, cohort study was performed in private infertility centre to evaluate the embryological and clinical results of a large exclusively SET program according to patient age (lower or equal 29, 30–34, 35–39, 40–44 and equal or higher 45 years).MaterialsA total of 7,244 infertile patients have undergone 20,244 cycles with a clomiphene-based minimal stimulation or natural cycle IVF protocol during 2008. Following oocyte retrieval, fertilization and embryo culture a total of 10,401 fresh or frozen single embryo transfer procedures were performed involving cleavage-stage embryos or blastocysts.ResultsSuccessful oocyte retrieval rate (78.0 %) showed no age-dependent decrease until 45 years. Fertilization (80.3 %) and cleavage (91.1 %) rates were not significantly different between age groups. Blastocyst formation (70.1 % to 22.8 %) and overall live birth rates (35.9 % to 2 %) showed an age-dependent decrease. Frozen-thawed blastocyst transfer cycles gave the highest chance of live birth per embryo transfer (41.3 % to 6.1 %).ConclusionsHigh fertilization and cleavage rates were obtained regardless of age whereas blastocyst formation and live birth rates showed an age-dependent decrease. An elective single embryo transfer program based on a minimal ovarian stimulation protocol yields acceptable live birth rates per embryo transfer in infertile patients up until their mid-forties. However in very advanced age patients (equal or higher 45 years old) success rates fall below 1 %.

Gonadotropin-releasing hormone agonists versus antagonists for controlled ovarian hyperstimulation in oocyte donors: a systematic review and meta-analysis.

OBJECTIVE To compare GnRH agonists and antagonists in oocyte-donation IVF treatment cycles by a systematic review and meta-analysis of trials. DESIGN Systematic review and meta-analysis of randomized clinical trials (RCT). Systematic literature searches were conducted, and all randomized trials that compared GnRH agonists with antagonists in oocyte-donation IVF treatment cycles were included. Study selection, quality appraisal, and data extractions were performed independently and in duplicate. SETTING Tertiary fertility center. PATIENT(S) A total of 1,024 oocyte donors treated in eight RCTs. INTERVENTION(S) Comparison of GnRH agonists versus antagonists in oocyte-donation IVF treatment. MAIN OUTCOME MEASURE(S) Ongoing pregnancy, oocytes retrieved, duration of stimulation, gonadotropin consumption, and ovarian hyperstimulation syndrome incidence (OHSS) per randomized oocyte donor. RESULT(S) Meta-analysis of these studies showed no significant difference in ongoing pregnancy rate between the GnRH agonists and antagonists (risk ratio [RR] 1.15, 95% confidence interval [CI] 0.97 to 1.36). The duration of stimulation was significantly lower with the GnRH antagonist protocol (weighed mean difference [WMD] -0.90 days, 95% CI -1.61 to -0.20). No significant differences were observed in the number of oocytes retrieved (WMD -0.60, 95% CI -2.26 to +1.07), gonadotropin consumption (WMD -264 IU, 95% CI -682 to +154), or OHSS incidence (RR 0.62, 95% CI 0.18 to 2.15). CONCLUSION(S) No significant differences were observed in ongoing pregnancy rate or the number of retrieved oocytes after donor stimulation with GnRH agonist or antagonist protocols.

Blastocyst culture is associated with an elevated incidence of monozygotic twinning after single embryo transfer.

In a 7-year (2002-2008) retrospective study of a large IVF program based on minimal ovarian stimulation and single ET (47,841 single ETs), monozygotic twinning occurred in 1.01% of 14,956 clinical pregnancies. Blastocyst culture was associated with a significantly increased monozygotic twinning risk (adjusted odds ratio, 2.04; 95% confidence interval, 1.29-4.48), whereas embryo freezing, type of stimulation protocol used, intracytoplasmic sperm injection fertilization, or zona removal did not influence its incidence.

Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte donation cycles: a randomised clinical trial

Aim. To compare donor and recipient outcome after inducing the final oocyte maturation with hCG or GnRH agonist in GnRH-antagonist treated oocyte donation (OD) cycles. Methods. Two-hundred fifty-seven oocyte donors were enrolled to participate in a clinical trial in a private fertility centre. After stimulation with 225 IU rFSH and Cetrorelix 0.25 mg/day, 212 oocyte donors were randomised with sealed envelopes for triggering with recombinant hCG (Ovitrelle 250 μgr, n = 106) or a GnRH agonist (triptorelin 0.2 mg, n = 106). Results. The number of retrieved COCs (12 ± 6.3 vs 11.4 ± 6.4), mature oocytes (8 ± 4.6 vs 7.5 ± 4.1), the proportion of mature oocytes (67.2 ± 20.4% vs 67.1 ± 20.9%) and fertilisation rates (67.8 ± 23.5% vs 71.1 ± 22.1%) were comparable. Clinical, ongoing pregnancy and live birth rates were not statistically different in the corresponding recipient groups. Nine cases of mild and one case of severe OHSS occurred in hCG group, whereas no cases were detected in GnRH agonist group. Conclusions. The findings of our RCT suggest that donor and recipient outcome are comparable in OD cycles triggered with hCG or a GnRH agonist. Furthermore, the risk of OHSS seems to be reduced considerably, therefore the combination of a GnRH antagonist protocol with GnRH agonist triggering constitutes a safe treatment option for egg-donors.

Transvaginal versus transabdominal ultrasound guidance for embryo transfer in donor oocyte recipients: a randomized clinical trial

OBJECTIVE To compare pregnancy and implantation rates with transvaginal (TV) versus transabdominal (TA) ultrasound-guided embryo transfer (ET). DESIGN Randomized, clinical trial registered at clinicaltrials.gov (NCT 01137461). SETTING Private, infertility clinic. PATIENT(S) Three-hundred thirty randomized recipients of donor oocytes. INTERVENTION(S) Embryo transfer using TV (with empty bladder, using the Kitazato ET Long catheter) versus TA ultrasound guidance (with full bladder, using the echogenic Sure View Wallace catheter). MAIN OUTCOME MEASURE(S) Overall pregnancy, clinical pregnancy, implantation, and ongoing pregnancy rates. Duration and difficulty of ET. Patient-reported uterine cramping and discomfort, as evaluated by questionnaire. RESULT(S) No statistically significant differences were observed in clinical pregnancy 50.9% versus 49.4% (95% confidence interval of the difference: -9.2 to +12.2%), implantation 34.5% versus 31.4% (95% CI of the difference: -4 to +10.3%) between the TV and TA ultrasound-guided groups. Transfer difficulty (6% versus 4.2%) and uterine cramping (27.2% versus 18.3%) were not statistically significantly different between treatment groups. Total duration (154±119 versus 85±76 seconds) was statistically significantly higher in the TV ultrasound group. Light to moderate-severe discomfort related to bladder distension was reported by 63% of the patients in the TA ultrasound group. CONCLUSION(S) Transvaginal ultrasound-guided ET yielded similar success rates compared with the TA ultrasound-guided procedure without requiring the assistance of a sonographer. It was associated with increased patient comfort due to the absence of bladder distension.

Early ovarian hyperstimulation syndrome is completely prevented by gonadotropin releasing-hormone agonist triggering in high-risk oocyte donor cycles: a prospective, luteal-phase follow-up study

In this prospective, follow-up study of 102 high-risk oocyte donors in their luteal phase, we found a complete absence of ovarian hyperstimulation syndrome (no signs of hemoconcentration or ascites) after the donors were triggered with a gonadotropin releasing-hormone (GnRH) agonist. Due to its powerful preventive effect, the GnRH antagonist protocol combined with a GnRH agonist trigger should preferentially be used in egg donors; in conjunction with an effective luteal support or embryo cryopreservation, the protocol could also be applied to high-risk in vitro fertilization patients.

Short-term, low-dose, non-steroidal anti-inflammatory drug application diminishes premature ovulation in natural-cycle IVF

A retrospective cohort study was conducted in a private infertility centre to evaluate the use of non-steroidal antiinflammatory drugs (NSAID) in natural-cycle IVF (nIVF) treatment. A total of 1865 first-rank nIVF cycles performed during 2009–2010 were evaluated. Low-dose, post-trigger NSAID was administered in a non-randomized way in cycles at higher ovulation risk where an imminent LH surge was detected on triggering day. Main outcome measures were premature ovulation rate, embryo transfer rate per scheduled cycle and clinical pregnancy and live birth rates per embryo transfer. NSAID use was associated with a significantly lower risk of premature ovulation (3.6% versus 6.8%, adjusted OR 0.24, 95% CI 0.15–0.39, P < 0.0001) and higher embryo transfer rate (46.8% versus 39.5%, adjusted OR 1.38, 95% CI 1.06–1.61, P = 0.012) per scheduled cycle. Clinical pregnancy (39.1% versus 35.9%) and live birth rates per embryo transfer (31.3% versus 31.4%) were comparable. In this retrospective series, short-term low-dose NSAID application positively influenced nIVF cycles by diminishing the rate of unwanted premature ovulations and increasing the proportion of cycles reaching embryo transfer.