Pregnancy and neonatal outcomes in fresh and frozen cycles using blastocysts derived from ovarian stimulation with follitropin delta.

PURPOSE: To describe the pregnancy and neonatal outcomes using fresh and vitrified/warmed blastocysts obtained from ovarian stimulation with follitropin delta in controlled trials versus follitropin alfa. METHODS: This investigation evaluated the outcome from 2719 fresh and frozen cycles performed in 1326 IVF/ICSI patients who could start up to three ovarian stimulations in the ESTHER-1 (NCT01956110) and ESTHER-2 (NCT01956123) trials, covering 1012 fresh cycles and 341 frozen cycles with follitropin delta and 1015 fresh cycles and 351 frozen cycles with follitropin alfa. Of the 1326 first cycle patients, 513 continued to cycle 2 and 188 to cycle 3, and 441 patients started frozen cycles after the fresh cycles. Pregnancy follow-up was continued until 4 weeks after birth. RESULTS: The overall cumulative take-home baby rate after up to three stimulation cycles was 60.3% with follitropin delta and 60.7% with follitropin alfa (-0.2% [95% CI: -5.4%; 5.0%]), of which the relative contribution was 72.8% from fresh cycles and 27.2% from frozen cycles in each treatment group. Across the fresh cycles, the ongoing implantation rate was 32.1% for follitropin delta and 32.1% for follitropin alfa, while it was 27.6% and 27.8%, respectively, for the frozen cycles. Major congenital anomalies among the live-born neonates up until 4 weeks were reported at an incidence of 1.6% with follitropin delta and 1.8% with follitropin alfa (-0.2% [95% CI: -1.9%; 1.5%]). CONCLUSIONS: Based on comparative trials, the pregnancy and neonatal outcomes from fresh and frozen cycles provide reassuring data on the efficacy and safety of follitropin delta. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01956110 registered on 8 October 2013; NCT01956123 registered on 8 October 2013.

Adverse obstetric and perinatal outcomes in 1,136 singleton pregnancies conceived after programmed frozen embryo transfer (FET) compared with natural cycle FET.

OBJECTIVE: To investigate whether obstetric and perinatal outcomes in pregnancies differ after different frozen embryo transfer (FET) protocols. DESIGN: Register-based cohort study. SETTING: Not applicable. PATIENT(S): All singleton deliveries after assisted reproductive technology in Denmark from 2006 to 2014. Data consisted of 1,136 deliveries after frozen in vitro fertilization. Frozen embryo transfer cycles were grouped by type of FET protocol: programmed FET (n = 357); modified natural cycle FET (n = 611); and true natural cycle FET (n = 168). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Obstetric outcomes (hypertensive disorders in pregnancy, preterm prelabor rupture of membranes, placenta previa, placental abruption, induction of labor, postpartum hemorrhage, and cesarean section) and perinatal outcomes (post-term birth, preterm birth, birth weight, small for gestational age, large for gestational age). RESULT(S): The risk of hypertensive disorders in pregnancy, postpartum hemorrhage, and cesarean section was significantly higher after programmed FET compared with natural cycle FET (modified natural cycle FET and true natural cycle FET). A higher risk of birth weight > 4,500 g was observed in the programmed FET group compared with natural cycle FET. CONCLUSION(S): This study shows that obstetric and perinatal outcomes are adversely affected in programmed FET cycles. Hence, when possible, an endometrial preparation with the creation of a corpus luteum should be considered. Properly sized randomized controlled trials of FET in programmed cycle versus natural cycle including perinatal outcomes are warranted in the future. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN11780826.

Effect of maternal age on maternal and neonatal outcomes after assisted reproductive technology.

OBJECTIVE: To compare the effect of maternal age on assisted reproductive technology (ART) and spontaneous conception (SC) pregnancies regarding maternal and neonatal complications. DESIGN: Nordic retrospective population-based cohort study. Data from national ART registries were cross-linked with national medical birth registries. SETTING: Not applicable. PATIENT(S): A total of 300,085 singleton deliveries: 39,919 after ART and 260,166 after SC. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Hypertensive disorders in pregnancy (HDP), placenta previa, cesarean delivery, preterm birth (PTB; <37 weeks), low birth weight (LBW; <2,500 g), small for gestational age (SGA), and perinatal mortality (≥28 weeks). Adjusted odds ratios (AORs) were calculated. Associations between maternal age and outcomes were analyzed. RESULT(S): The risk of placenta previa (AOR 4.11-6.05), cesarean delivery (AOR 1.18-1.50), PTB (AOR 1.23-2.19), and LBW (AOR 1.44-2.35) was significantly higher in ART than in SC pregnancies for most maternal ages. In both ART and SC pregnancies, the risk of HDP, placenta previa, cesarean delivery, PTB, LBW, and SGA changed significantly with age. The AORs for adverse neonatal outcomes at advanced maternal age (>35 years) showed a greater increase in SC than in ART. The change in risk with age did not differ between ART and SC for maternal outcomes at advanced maternal age. CONCLUSION(S): Having singleton conceptions after ART results in higher maternal and neonatal outcome risks overall, but the impact of age seems to be more pronounced in couples conceiving spontaneously.

Perinatal outcomes in 375 children born after oocyte donation: a Danish national cohort study.

OBJECTIVE: To describe perinatal outcomes in children born after oocyte donation (OD) compared with in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and spontaneous conception (SC). DESIGN: National cohort study. SETTING: Fertility clinics. PATIENT(S): Three hundred seventy-five children born after OD during the period 1995-2010. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mean birth weight, mean gestational age, risks of low birth weight (LBW), preterm birth (PTB), congenital malformations, cesarean delivery, preeclampsia, and admittance to neonatal intensive care unit. RESULT(S): We found an increased risk of PTB in OD pregnancies. The adjusted odds ratio (AOR) of PTB in OD singletons was 1.8 (95% CI, 1.2-2.69), 2.5 (95% CI, 1.7-3.6), and 3.4 (95% CI, 2.3-4.9) compared with IVF, ICSI, and SC, respectively. The risk of LBW was also increased. The AOR of LBW was 1.4 (95% CI, 0.9-2.2), 1.8 (95% CI, 1.2-2.8), and 2.6 (95% CI, 1.7-4.0) compared with IVF, ICSI, and SC. The risk of preeclampsia was increased in OD pregnancies with an AOR of 2.9 (95% CI, 1.8-4.6), 2.8 (95% CI, 1.7-4.5), and 3.1 (95% CI, 1.9-4.9) compared with IVF, ICSI, and SC. After additional adjustment for preeclampsia, perinatal outcome improved. Among the twins, the difference between the groups was less pronounced. CONCLUSION(S): Pregnancies after OD have a poorer perinatal outcome than those after standard IVF and ICSI mainly because of the high prevalence of preeclampsia.

Infant outcome of 957 singletons born after frozen embryo replacement: the Danish National Cohort Study 1995-2006.

OBJECTIVE: To examine infant outcome of singletons born after cryopreservation of embryos (Cryo). DESIGN: National population-based controlled follow-up study. SETTING: Denmark, 1995-2007. PATIENT(S): The study population was 957 Cryo singletons (Cryo-IVF, n=660; Cryo-ICSI, n=244; Cryo-IVF/-ICSI, n=53). The first control group was all singletons born after fresh IVF or intracytoplasmic sperm injection (ICSI) during the same period (IVF, n=6904; ICSI, n=3425). The second control group comprised a random sample of non-assisted reproductive technology (ART) singletons (n=4800). INTERVENTION(S): All observations were obtained from national registers. MAIN OUTCOME MEASURE(S): Low birth weight (LBW; <2500 g), preterm birth (PTB; <37 weeks), congenital malformations, mortality, and morbidity. RESULT(S): Birth weight was higher in Cryo (mean=3578 g, SD=625) versus fresh (mean=3373 g, SD=648) and in Cryo versus non-ART (mean=3537 g, SD=572), and this was also the case for first birth only. Lower adjusted risk of LBW (odds ratio [OR]=0.63; 95% confidence interval [CI], 0.45-0.87) and PTB (OR=0.70; 95% CI, 0.53-0.92) was observed in Cryo versus fresh. Similar LBW and PTB rates were observed when comparing Cryo with non-ART, but the perinatal mortality rate was doubled in Cryo (1.6%) compared with non-ART (0.8%) singletons, and the adjusted risks of very preterm birth (<34 weeks) and neonatal admittance were also significantly increased. No significant differences in the prevalence rates of birth defects, neurological sequelae, malignancies, and imprinting-related diseases were observed between the Cryo and the two control groups. However higher malformation and cerebral palsy rates were observed in the total Fresh vs. non-ART group. CONCLUSION(S): Cryo singletons have better neonatal outcome than offspring after fresh ET but poorer compared with non-ART singletons.