Improve In Vitro Fertilization Outcomes Research Articles

Preimplantation genetic screening (PGS) still in search of a clinical application: a systematic review

Only a few years ago the American Society of Assisted Reproductive Medicine (ASRM), the European Society for Human Reproduction and Embryology (ESHRE) and the British Fertility Society declared preimplantation genetic screening (PGS#1) ineffective in improving in vitro fertilization (IVF) pregnancy rates and in reducing miscarriage rates. A presumably upgraded form of the procedure (PGS#2) has recently been reintroduced, and is here assessed in a systematic review. PGS#2 in comparison to PGS#1 is characterized by: (i) trophectoderm biopsy on day 5/6 embryos in place of day-3 embryo biopsy; and (ii) fluorescence in-situ hybridization (FISH) of limited chromosome numbers is replaced by techniques, allowing aneuploidy assessments of all 24 chromosome pairs. Reviewing the literature, we were unable to identify properly conducted prospective clinical trials in which IVF outcomes were assessed based on “intent to treat”. Whether PGS#2 improves IVF outcomes can, therefore, not be determined. Reassessments of data, alleged to support the efficacy of PGS#2, indeed, suggest the opposite. Like with PGS#1, the introduction of PGS#2 into unrestricted IVF practice again appears premature, and threatens to repeat the PGS#1 experience, when thousands of women experienced reductions in IVF pregnancy chances, while expecting improvements. PGS#2 is an unproven and still experimental procedure, which, until evidence suggests otherwise, should only be offered under study conditions, and with appropriate informed consents.

In Vitro Fertilization Outcomes Following Assisted Hatching of Embryos with Thick Zona Pellucida—A Prospective Randomized Study

Purpose: Impaired hatching is associated with implantation failure following in vitro fertilization (IVF). Thickening or hardening of the zona pellucida (ZP) has been proposed as a factor in this impairment. We examined whether selective assisted hatching (AH) is beneficial with embryos having a thick ZP. Methods: This prospective, randomized controlled study was performed in the IVF unit of an obstetrics and gynecology department in a university-affiliated hospital. Only patients undergoing IVF and having a ZP thickness of ≥17 μm measured in all their embryos were included. In the intervention group, AH was applied to all embryos, before their transfer. In the control group, embryos were transferred without AH. Implantation, clinical pregnancy and live birth rates were the study endpoints. Results: Both study arms were comparable in most baseline parameters. The two groups did not differ in implantation rates (14.1% control vs. 8.92% intervention, odds ratio (OR) = 0.5974, 95% confidence interval (CI) 0.325 - 1.1), clinical pregnancy rates (36.7% vs. 25.8%, OR = 0.6025, 95% CI 0.274 - 1.325), or live birth rates (25% vs. 18.9%, OR = 0.7021, 95% CI 0.291 - 1.691). Conclusions: Selecting embryos for AH by their ZP thickness as a sole parameter was not found to be beneficial and to improve IVF outcome.

Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial

To determine whether blastocyst biopsy and rapid quantitative real-time polymerase chain reaction (qPCR)-based comprehensive chromosome screening (CCS) improves in vitro fertilization (IVF) implantation and delivery rates. Randomized controlled trial. Academic reproductive medicine center. Infertile couples in whom the female partner (or oocyte donor) is between the ages of 21 and 42 years who are attempting conception through IVF. Embryonic aneuploidy screening. Sustained implantation and delivery rates. We transferred 134 blastocysts to 72 patients in the study (CCS) group and 163 blastocysts to 83 patients in the routine care (control) group. Sustained implantation rates (probability that an embryo will implant and progress to delivery) were statistically significantly higher in the CCS group (89 of 134; 66.4%) compared with those from the control group (78 of 163; 47.9%). Delivery rates per cycle were also statistically significantly higher in the CCS group. Sixty one of 72 treatment cycles using CCS led to delivery (84.7%), and 56 of 83 (67.5%) control cycles ultimately delivered. Outcomes were excellent in both groups, but use of CCS clearly improved patient outcomes. Blastocyst biopsy with rapid qPCR-based comprehensive chromosomal screening results in statistically significantly improved IVF outcomes, as evidenced by meaningful increases in sustained implantation and delivery rates. NCT01219283.

Transvaginal ovarian drilling (TVOD) for severe polycystic ovary syndrome (PCOS) prior to in vitro fertilization (IVF) dramatically improves IVF outcomes

Transvaginal ovarian drilling (TVOD) for severe polycystic ovary syndrome (PCOS) prior to in vitro fertilization (IVF) dramatically improves IVF outcomes

Integration of Sperm Motility and Chemotaxis Screening with a Microchannel-Based Device

Sperm screening is an essential step in in vitro fertilization (IVF) procedures. The swim-up method, an assay for sperm motility, is used clinically to select the ideal sperm for subsequent manipulation. However, additional parameters, including acrosome reaction capability, chemotaxis, and thermotaxis, are also important indicators of mammalian sperm health. To monitor both sperm motility and chemotaxis simultaneously during sperm screening, we designed and constructed a microdevice comprising a straight channel connected with a bibranch channel that mimics the mammalian female reproductive tract. The width and length of the straight channel were optimized to select the motile sperms. We selectively cultured cumulus cells in the bibranch channel to generate a chemoattractant-forming chemical gradient. Sperm chemotaxis was represented by the ratio of the sperm swimming toward different branches. The percentage of motile sperms improved from 58.5% (3.8%) to 82.6% (2.9%) by a straight channel 7 mm in length and 1 mm in width. About 10% of sperms were found to be chemotactically responsive in our experiment, which is consistent with previous studies. For the first time, we achieved the combined evaluation of both sperm motility and chemotaxis. The motile and chemotactically responsive sperms can easily be enriched on a lab-on-a-chip device to improve IVF outcome.

Day 4 embryo transfer improves IVF outcomes compared with day 3 embryo transfer

OBJECTIVE: Even though the majority of embryos are transferred on day 3 following in vitro fertilization (IVF), the morphological assessment of day 3 embryos may not accurately predict further developmental competency and pregnancy potential. We compared the clinical outcomes of day 4 ET cycles with day 3 ET cycles in both fresh IVF-ET and frozen-thawed ET cycles (FET) to assess whether day 4 ET improves clinical outcomes.DESIGN: Retrospective study.MATERIALS AND METHODS: Total 759 fresh IVF-ET (660 on day 3 and 99 on day 4) cycles and 261 frozen-thawed ET (231 on day 3 and 30 on day 4) cycles were analyzed retrospectively during the period from Jan. 2006 to Aug. 2007. In this study, to avoid unbiased comparison regard to embryo quality, we selected the ET cycles which have at least one good quality 8-cell stage embryo on day 3. Clinical outcomes were evaluated in day 3 and day 4 ET cycles. Chi-square test or t-test was used for statistical analysis, and P values of < 0.05 were considered significant.RESULTS: There were no differences in clinical parameters between two groups. The mean number of transferred embryos on day 4 ET cycles was significantly lower than that of day 3 ET cycles (3.1 ± 0.7 vs. 3.3 ± 0.7, p < 0.01). In fresh IVF-ET cycles, day 4 ET cycles showed significantly higher IR (26.2% vs. 19.8%, p < 0.01) and CPR (56.6% vs. 45.5%) compared with day 3 ET cycles. In frozen-thawed ET cycles, survival rates and mean number of transferred embryos were similar between two groups. CPR and IR of frozen-thawed day 4 ET cycles were significantly higher than those of frozen-thawed day 3 ET cycles (70.0% vs. 45.5% and 31.3% vs. 19.6%, p < 0.05).CONCLUSIONS: Day 4 ET cycles showed higher pregnancy outcomes compared with day 3 ET cycles. These results suggest that day 4 ET more synchronized with in vivo reproductive processes than day 3 ET. OBJECTIVE: Even though the majority of embryos are transferred on day 3 following in vitro fertilization (IVF), the morphological assessment of day 3 embryos may not accurately predict further developmental competency and pregnancy potential. We compared the clinical outcomes of day 4 ET cycles with day 3 ET cycles in both fresh IVF-ET and frozen-thawed ET cycles (FET) to assess whether day 4 ET improves clinical outcomes. DESIGN: Retrospective study. MATERIALS AND METHODS: Total 759 fresh IVF-ET (660 on day 3 and 99 on day 4) cycles and 261 frozen-thawed ET (231 on day 3 and 30 on day 4) cycles were analyzed retrospectively during the period from Jan. 2006 to Aug. 2007. In this study, to avoid unbiased comparison regard to embryo quality, we selected the ET cycles which have at least one good quality 8-cell stage embryo on day 3. Clinical outcomes were evaluated in day 3 and day 4 ET cycles. Chi-square test or t-test was used for statistical analysis, and P values of < 0.05 were considered significant. RESULTS: There were no differences in clinical parameters between two groups. The mean number of transferred embryos on day 4 ET cycles was significantly lower than that of day 3 ET cycles (3.1 ± 0.7 vs. 3.3 ± 0.7, p < 0.01). In fresh IVF-ET cycles, day 4 ET cycles showed significantly higher IR (26.2% vs. 19.8%, p < 0.01) and CPR (56.6% vs. 45.5%) compared with day 3 ET cycles. In frozen-thawed ET cycles, survival rates and mean number of transferred embryos were similar between two groups. CPR and IR of frozen-thawed day 4 ET cycles were significantly higher than those of frozen-thawed day 3 ET cycles (70.0% vs. 45.5% and 31.3% vs. 19.6%, p < 0.05). CONCLUSIONS: Day 4 ET cycles showed higher pregnancy outcomes compared with day 3 ET cycles. These results suggest that day 4 ET more synchronized with in vivo reproductive processes than day 3 ET.

A prospective study to evaluate whether gonadotropin releasing hormone (GnRH) antagonists have an adverse effect on embryo implantation

A prospective study to evaluate whether gonadotropin releasing hormone (GnRH) antagonists have an adverse effect on embryo implantation

Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors

Objective: To determine if metformin therapy improves in vitro fertilization (IVF) outcomes in patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). Design: Retrospective data analysis of selective groups of patients. Setting: A private IVF unit. Patient(s): Forty-six women with clomiphene citrate–resistant PCOS underwent 60 cycles of IVF embryo transfer with intracytoplasmic sperm injection. Intervention(s): In half of the cycles, patients received metformin (1000 to 1500 mg) daily, starting the cycle prior to gonadotropin treatment. Main Outcome Measure(s): Total number of follicles; serum estradiol (E 2) on the day of hCG administration and the cycle’s E 2 maximum; total number of oocytes, mature oocytes, embryos, fertilization, and pregnancy rates; and follicular fluid levels of insulin-like growth factors (IGF-I, IGF-II) and IGF-binding proteins (IGFBP-1, IGFBP-3). Result(s): In patients treated with metformin, the total number of follicles on the day of hCG treatment was decreased (23 ± 1.2 vs. 33 ± 2.6) with no change in follicles ≥14 mm in diameter (21 ± 1.2 vs. 25 ± 1.7). Metformin treatment did not affect the mean number of oocytes retrieved (22 ± 1.9 vs. 20.3 ± 1.5). However, the mean number of mature oocytes (18.4 ± 1.5 vs. 13 ± 1.5) and embryos cleaved (12.5 ± 1.5 vs. 5.9 ± 0.9) were increased after metformin treatment. Fertilization rates (64% vs. 43%) and clinical pregnancy rates (70% vs.30%) were also increased. Metformin led to modulation of preovulatory of follicular fluid IGF levels with increases of IGF-I (140 ± 8 vs. 109 ± 7ng/mL) and decreased of IGFBP-1 (133 ± 8 vs.153 ± 9ng/mL). Conclusion(s): Metformin use appears to improve IVF outcomes in patients with clomiphene citrate–resistant PCOS.

Multivariate analysis of factors predictive of successful live births in in vitro fertilization (IVF) suggests strategies to improve IVF outcome.

Our purpose was (1) to identify characteristics correlated with pregnancy outcome, (2) to use these characteristics to predict in vitro fertilization (IVF) outcome, and (3) to develop strategies that might improve IVF success. Maternal age, cause for IVF, donor insemination, rank of attempt, serum estradiol and luteinizing hormone levels on the day of human chorionic gonadotropin administration, flexible vs rigid catheter, number of embryos transferred of each morphologic type, and cell number were analyzed by logistic regression. Variables positively correlated with success are as follows: (1) for pregnancy, endometriosis and 2-, 3-, and 4-cell good and 4-cell excellent embryos; (2) for live births, 2-, 3-, and 4-cell good and 4-cell excellent embryos and donor insemination; and (3) for multiple births, 2- and 4-cell good and 4-cell excellent embryos. Maternal age was negatively correlated with live births. Embryos derived from IVF have different potentials for implantation, live births, and multiple births. Transferring one additional good-quality embryo for each 5 years of incremental increase in maternal age is predicated to improve live birth rates without increasing multiple births.

No beneficial effects of human growth hormone therapy in normal ovulatory patients with a poor ovarian response to gonadotropins.

We studied the effects of human growth hormone (hGH) in 7 in vitro fertilization (IVF) patients with normal ovulatory menstrual cycles who showed a low response to ovarian stimulation with follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG). Human growth hormone therapy had no significant effect on the number of days of gonadotropic stimulation, on the total amount of hMG administered, on the serum estradiol level on the day of human chorionic gonadotropin injection, or on the IVF outcome. Our preliminary results do not encourage the routine use of hGH to improve IVF outcome in normogonadotropic ovulatory patients who respond poorly to the standard FSH/hMG protocol.

The effect of pituitary suppression and the women's age on embryo viability and uterine receptivity

To examine the effect of pituitary suppression and the women's age on embryo viability and uterine receptivity.Retrospective analysis of 394 embryo transfers (ET) after in vitro fertilization (IVF).Community hospital IVF program from 1986 to 1990.Three groups were studied: women less than 40 years with pituitary suppression (group 1) and without pituitary suppression (group 2); women 40 years of age and older with pituitary suppression (group 3).Pituitary suppression was achieved in groups 1 and 3 with daily leuprolide acetate starting in the luteal phase; human menopausal gonadotropin and progesterone were given intramuscularly.Ongoing and multiple ongoing pregnancy rates (PRs) were compared in the three groups. A mathematical model of implantation was used to estimate embryo viability and uterine receptivity.Ongoing and multiple ongoing PRs per ET in group 1 (28.6% and 12.3%) were significantly higher than the corresponding rates in group 2 (16.9% and 2.4%) and in group 3 (16.9% and 3.4%). Implantation analysis revealed higher embryo viability without change in uterine receptivity with pituitary suppression (group 1 versus 2). Decrease in both embryo viability and uterine receptivity was noted in women greater than 40 (group 1 versus 3).(1) Pituitary suppression improved implantation outcome by increasing embryo viability with no change in uterine receptivity and was associated with a high multiple PR in women less than 40; (2) in women greater than 40 both embryo viability and, to a lesser extent, uterine receptivity were decreased; (3) transfer of a larger number of embryos in older patients may improve IVF outcome without excessive risk of multiple pregnancy.

The effect of pituitary suppression and the women’s age on embryo viability and uterine receptivity

To examine the effect of pituitary suppression and the women's age on embryo viability and uterine receptivity. Retrospective analysis of 394 embryo transfers (ET) after in vitro fertilization (IVF). Community hospital IVF program from 1986 to 1990. Three groups were studied: women less than 40 years with pituitary suppression (group 1) and without pituitary suppression (group 2); women 40 years of age and older with pituitary suppression (group 3). Pituitary suppression was achieved in groups 1 and 3 with daily leuprolide acetate starting in the luteal phase; human menopausal gonadotropin and progesterone were given intramuscularly. Ongoing and multiple ongoing pregnancy rates (PRs) were compared in the three groups. A mathematical model of implantation was used to estimate embryo viability and uterine receptivity. Ongoing and multiple ongoing PRs per ET in group 1 (28.6% and 12.3%) were significantly higher than the corresponding rates in group 2 (16.9% and 2.4%) and in group 3 (16.9% and 3.4%). Implantation analysis revealed higher embryo viability without change in uterine receptivity with pituitary suppression (group 1 versus 2). Decrease in both embryo viability and uterine receptivity was noted in women greater than 40 (group 1 versus 3). (1) Pituitary suppression improved implantation outcome by increasing embryo viability with no change in uterine receptivity and was associated with a high multiple PR in women less than 40; (2) in women greater than 40 both embryo viability and, to a lesser extent, uterine receptivity were decreased; (3) transfer of a larger number of embryos in older patients may improve IVF outcome without excessive risk of multiple pregnancy.