A prospective randomized controlled trial of preimplantation genetic screening in the "good prognosis" patient. Preimplantation genetic screening in women of advanced maternal age caused a decrease in clinical pregnancy rate: a randomized controlled trial. What next for preimplantation genetic screening (PGS)? Experience with blastocyst biopsy and testing for aneuploidy. Preimplantation genetic screening for aneuploidy of embryos after in vitro fertilization in women aged at least 35 years: a prospective randomized trial. Effects of prostaglandin treatment and paracervical blockade on postoperative pain in patients undergoing first trimester abortion in general anesthesia. Blastocyst-stage versus cleavage-stage embryo transfer in women with high oestradiol concentrations: randomized controlled trial. Preimplantation genetic screening does not improve delivery rate in women under the age of 36 following single-embryo transfer. Evaluation of two doses of recombinant luteinizing hormone supplementation in an unselected group of women undergoing follicular stimulation for in vitro fertilization.
To determine whether the routine use of preimplantation genetic screening (PGS) in "good prognosis" women improves in vitro fertilization (IVF) cycle outcome.
                Randomized, controlled, prospective clinical study.
                Private infertility clinic.
                Infertile women predicted to have a good prognosis as defined by: age <39 years, normal ovarian reserve, body mass index <30 kg/m(2), presence of ejaculated sperm, normal uterus, <or=2 previous failed IVF cycles.
                Patients were randomized to the PGS group or the control group on day 3 after oocyte retrieval; 23 women underwent blastomere biopsy on day 3 after fertilization (PGS group), and 24 women underwent routine IVF (control group). All embryos were transferred on day 5 or 6 after fertilization.
                Pregnancy, implantation, multiple gestation, and live birth rates.
                No statistically significant differences were found between the PGS and control groups with respect to clinical pregnancy rate (52.4% versus 72.7%). However, the embryo implantation rate was statistically significantly lower for the PGS group (31.7% versus 62.3%) as were the live birth rate (28.6% versus 68.2%) and the multiple birth rate (9.1% versus 46.7%).
                In a "good prognosis" population of women, PGS does not appear to improve pregnancy, implantation, or live birth rates. Advanced maternal age (AMA) is an important parameter that negatively influences the clinical pregnancy rate in IVF, in particular owing to the increased embryo aneuploidy rate. It has thus been suggested that only transferring euploid embryos in this patient group would improve the pregnancy rate. The purpose of this study was to test whether employing preimplantation genetic screening (PGS) in AMA patients would increase the clinical pregnancy rate.
                We conducted a two-center, randomized controlled trial (RCT) to analyze the outcome of embryo transfers in AMA patients (>or=38 years of age) after PGS using FISH analysis for chromosomes X, Y, 13, 16, 18, 21 and 22. The PGS group was compared with a control group. The primary outcome measure was clinical pregnancy rate after 6-7 weeks of gestation per randomized patient.
                The study was terminated early as an interim analysis showed a very low conditional power of superiority for the primary outcome. Of the 320 patients calculated to be included in the study, 56 and 53 patients were randomized into the PGS and control groups, respectively. The clinical pregnancy rate in the PGS group was 8.9% (95% CI, 2.9-19.6%) compared with 24.5% (95% CI, 13.8-38.3%) in the control group, giving a difference of 15.6% (95% CI, 1.8-29.4%, P = 0.039).
                Although the study was terminated early, this RCT study provides evidence against the use of PGS for AMA patients when performing IVF. Trial registration number: ISRCTN38014610. Blastocysts more commonly have a normal karyotype than cleavage-stage embryos do. Moreover, blastocysts have also made a metabolic transition from catabolism and recycling of the oocyte's reserves and resources, processes that fuel the first 3 days of cleavage. Although not all blastocysts are karyotypically equal, it is still to be determined to what extent a mosaic karyotype might be a normal feature among embryos, both at the cleavage stage and the blastocyst stage--and when looking for karyotypic abnormalities by embryo biopsy might help the chance of implantation rather than harm it. It is also still impractical to look at all the chromosomes that can, through their aneuploidy, stand in the way of successful embryonic and fetal development. We report a randomized clinical trial of blastocyst biopsy followed by preimplantation genetic screening (PGS) for aneuploidy using 5-colour FISH. The trial was suspended and then terminated early when we were unable to show an advantage for PGS. If we are correct in assuming that mitotic non-disjunction is common by the stage of the blastocyst (and that it is much less ominous than meiotic non-disjunction), then further studies of effective PGS of blastocysts for aneuploidy require methods of analysis that cover all the chromosomes and can differentiate the triallelic and monoallelic states of meiotically derived aneuploidies from the biallelic state of mitotic aneuploidies. To test the hypothesis that patients with advanced maternal age (AMA) have a higher implantation rate (IR) after embryo transfer of embryos with a normal chromosomal pattern for the chromosomes studied with preimplantation genetic screening (PGS) compared with patients who had an embryo transfer without PGS.
                Prospective randomized controlled trial (RCT).
                Academic tertiary setting.
                Patients with AMA (> or =35 years).
                In an RCT, the clinical IR per embryo transferred was compared after embryo transfer on day 5 or 6 between the PGS group (analysis of chromosomes 13, 16, 18, 21, 22, X, and Y) and the Control group without PGS.
                No differences were observed between the PGS group and the Control group for the clinical IR (15.1%; 14.9%; rate ratio 1.01; exact confidence interval [CI], 0.25-5.27), the ongoing IR (at 12 weeks) (9.4%; 14.9%), and the live born rate per embryo transferred (9.4%; 14.9%; rate ratio 0.63; exact CI, 0.08-3.37). Fewer embryos were transferred in the PGS group (1.6 +/- 0.6) than in the Control group (2.0 +/- 0.6). A normal diploid status was observed in 30.3% of the embryos screened by PGS.
                In this RCT, the results did not confirm the hypothesis that PGS results in improved reproductive outcome in patients with AMA.
                Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. The postoperative analgesic efficacy of a paracervical blockade (PCB) as an adjunct to general anesthesia (GA) during outpatient abortion (dilatation and curettage) is unclear, and the present study was initiated to evaluate if PCB is of significant importance per- or postoperatively.
                Two hundred women (aged 18-49 years) were assigned to one of four groups; group 1 received vaginal prostaglandin (PG) (PGE1, gemeprost 1 mg) for softening of the cervix preoperatively and surgery was performed in GA, group 2 received preoperative PG and surgery was performed in GA + PCB; group 3 did not receive PG treatment and surgery was performed in GA and group 4 were subjected to GA + PCB without preoperative PG.
                Women receiving preoperative prostaglandin treatment (groups 1 and 2) reported significantly higher pain intensity already preoperatively, but also postoperatively as compared to patients not treated with PG. The patients subjected to prostaglandin treatment (groups 1 and 2) also had a significantly higher consumption of analgesics as compared to non-PG treated groups (3 and 4). The addition of PCB did not influence pre- and postoperative pain intensity significantly or consumption of analgesics. Patients receiving PG also reported significantly more nausea than the others although nausea was of low intensity. Patients receiving PG were, however, discharged earlier than the others from the hospital.
                Preoperative treatment of the cervix with prostaglandins was associated with significantly higher pain intensity both pre- and postoperatively, and increased need for analgesics postoperatively and more intense nausea. PCB given just before surgery did not result in significant postoperative analgesia. More efficient techniques for pain control should be developed for women subjected to first trimester abortion with preoperative PG treatment. This prospective, randomized, controlled trial tested the hypothesis that delaying embryo transfer to the blastocyst stage can increase the probability of clinical pregnancy and live birth in women with high oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) undergoing intracytoplasmic sperm injection using the long protocol. A total of 200 women with oestradiol >3000 pg/ml on the HCG day with four or more good-quality, day-3 embryos were randomized in a 1:1 ratio to undergo day-3 or day-5 embryo transfer. Clinical pregnancy rates (CPR; 41% versus 59%; relative risk 0.70, 95% CI 0.52–0.93) and ongoing pregnancy/live-birth rates (35% versus 52%; relative risk 0.67, 95% CI 0.46–0.93) were lower in women undergoing cleavage-stage than blastocyst-stage embryo transfer. Using receiver operating characteristic curves, among women undergoing cleavage-stage embryo transfer, a detrimental cut-off value for not achieving pregnancy for oestradiol was 4200 pg/ml, with lower CPR and ongoing pregnancy/live-birth rates (P = 0.006 and 0.02, respectively). No detrimental cut-off value for oestradiol was identified among women undergoing blastocyst-stage embryo transfer. Delaying embryo transfer to the blastocyst stage can increase the probability of pregnancy in women with high oestradiol on the HCG day
                Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. Single-embryo transfer is a well-accepted strategy to avoid multiple pregnancies in an assisted reproductive technology (ART) programme. Besides the morphological quality and embryo kinetics up to the blastocyst stage, preimplantation genetic screening (PGS) of aneuploidy has been advocated as an adjuvant approach to select the embryo.
                Couples with a female partner younger than 36 were randomly assigned to undergo transfer of a single blastocyst in a cycle with or without PGS using FISH for the chromosomes X, Y, 13, 16, 18, 21, 22.
                After the enrolment of 120 of the projected 447 patients in each group, study recruitment was terminated prematurely on the basis of futility. The observed live birth delivery rates after ART were 30.8 versus 30.8% per randomized patient, 34.6 versus 34.6% per cycle initiated, 37.8 versus 37.0% per aspirated cycle and 41.6 versus 43.5% per embryo transfer for the control versus the PGS group, respectively, with absolute between-group differences (95% CI; P value) of 0% (-11.7 to 11.7; P = 1.00), 0% (-12.7 to 12.7; P = 1.00), -0.8% (-14.2 to 12.7; P = 0.91) and 2.1% (-12.7 to 16.7; P = 0.79), respectively. Even in this younger age group, only 61% of the embryos had a normal diploid status.
                The absence of a beneficial treatment effect in this randomized clinical trial provides no arguments in favour of PGS to improve live birth delivery rate following single-embryo transfer in women under the age 36. Clinical Trials.gov: NCT00670059. To evaluate the efficacy of two doses of recombinant (r)LH, 75 IU (recommended) or 37.5 IU, for follicular stimulation and outcomes in a randomized cohort of IVF patients.
                Randomized, prospective analysis.
                Private hospital incorporating an established IVF center.
                Women undergoing IVF who had a body mass index >18 or <35 and no abnormal karyotype, anovulation, oligomenorrhea, or any known endocrinopathy/illness.
                Pituitary desensitization was achieved with triptorelin (0.1 mg SC), and gonadotropin stimulation was performed with either rFSH alone (group A) or in combination with rLH in one of two doses: 37.5 IU (group B) or 75 IU (group C), daily.
                A range of endocrinologic, embryologic, clinical, and outcome parameters were evaluated.
                With rLH supplementation there was a significant increase in the incidence of implantation (9% for rFSH only [group A] vs. 11% and 16% with 37.5 IU rLH and 75.0 IU rLH [groups B and C], respectively) and clinical pregnancy (19% vs. 23% and 31%) (P<.01 and P<.04, respectively), whereas there was no difference in the multiple pregnancy rates. There was a significant (P<.001) increase in the total units of rFSH used in proportion to the amount of rLH supplementation (2,645 U vs. 3,475 U and 3,681 U) and in the level of peripheral E(2) on the day of hCG administration (1,049 pg/mL vs. 1,640 pg/mL and 1,226 pg/mL) (P<.001). There was no significant between difference in mean age, numbers of oocytes recovered, basal and downregulation hormone levels, or the incidence of fertilization in the absence or presence of rLH supplementation, but a higher incidence of grade 1 to 2 embryos was observed when rLH was supplemented.
                After pituitary desensitization, there was an increase in the incidence of implantation, clinical pregnancy, and delivery rates in patients stimulated with rFSH supplemented with rLH.
PGS as currently performed significantly decreases live birth rates in women of advanced maternal age and those with repeated IVF failure. Trials in which PGS was offered to women with a good prognosis suggested similar outcomes. PGS technique development is still ongoing in an effort to increase its efficacy. This involves biopsy at other stages of development (polar body or trophectoderm biopsy) and other methods of analysis (comparative genome hybridisation (CGH) or array-based technologies) than used by the trials included in this review. These new developments should be properly evaluated before their routine clinical application. Until such trials have been performed, PGS should not be offered as routine patient care in any form.