Enhancement of outcome from intracytoplasmic sperm injection: does co-culture or assisted hatching improve implantation rates? Short coincubation of gametes in in vitro fertilization improves implantation and pregnancy rates: a prospective, randomized, controlled study. The effects of brief gamete co-incubation in human in vitro fertilization. A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program. Clinical pregnancy and male subfertility; the ESHRE multicentre trial on the treatment of male subfertility. European Society of Human Reproduction and Embryology. Efficacy of double intrauterine insemination in controlled ovarian hyperstimulation cycles. Fallopian tube sperm perfusion versus intrauterine insemination in unexplained infertility: a randomized, prospective, cross-over trial.
In two separate prospectively randomized trials, intracytoplasmic sperm injection (ICSI) cycles were studied in a controlled manner to monitor the effects of either bovine oviductal epithelial cell co-culture (n = 119) or assisted hatching by zona drilling (n = 100). In the first study, immediately following ICSI, all eggs were placed directly either onto partial monolayers of bovine oviductal cells or into regular culture medium. Although the embryo developmental rate was apparently compromised in part by the presence of the co-culture cells, ultimately there were no significant differences in either the viable pregnancy rate (31.6% co-culture versus 29.0% control) or the embryonic implantation rate (11.4% co-culture versus 13.6% control). Assisted hatching also had no significant impact on ICSI cycle outcome in terms of either the viable pregnancy rate (30.0% assisted hatching versus 32.0% control) or the embryonic implantation rate (8.5% assisted hatching versus 13.5% control). However, in female patients aged > or = 35 years, assisted hatching appeared to convey a marginally significant benefit in terms of both the viable pregnancy rate (35.5% assisted hatching versus 11.1% control) and the embryonic implantation rate (10.3% assisted hatching versus 3.1% control). It seems that the overall improvement of ICSI cycle outcome cannot be achieved by the general application of either co-culture or assisted hatching. Nevertheless, it is possible that there remain specific patient groups that might benefit from selected use of either of these modalities. To examine the benefits of short coincubation of gametes compared to prolonged incubation in in vitro fertilization (IVF).
                Prospective randomized controlled study.
                Hospital-based fertility center.
                One hundred thirty patients (group 1) and 129 patients (group 2).
                Oocytes from group 1 were exposed to spermatozoa for 2 hours, and oocytes from group 2 were exposed to spermatozoa for 20 hours.
                Fertilization and cleavage rates, embryo quality, and pregnancy and implantation rates were evaluated. Estradiol (E(2)) and progesterone (P(4)) levels were measured in the wells of culture dishes after 2-hour exposure of oocytes/zygotes to spermatozoa in group 1 and after 20-hour exposure in both the groups.
                There was no difference between the two groups in the fertilization rate and the number of embryos obtained. However, the proportion of grade 1 embryos was significantly higher among group 1 compared to group 2 patients. Clinical pregnancy and implantation rates were significantly higher among group 1 compared to group 2. The significantly higher levels of E(2) and P(4) in the 20-hour cultures compared with the 2-hour cultures may have been detrimental to embryo quality, pregnancy, and implantation rates.
                Coincubation of gametes for 2 hours with standard or high insemination concentrations of spermatozoa significantly improved embryo quality and the pregnancy and implantation rates compared with overnight incubation of gametes. To investigate whether very short exposure of mature oocytes to sperm in vitro may affect the fertilization rates, embryo cleavage rates, and embryo quality between sibling oocytes in the same patient.
                Sibling oocytes of the same patient from 23 oocyte collection cycles were randomly allocated to the study group, with a 1-hr or 3-hr sperm-oocyte incubation, or the control group with the standard overnight gamete co-incubation. The fertilization rates, cleavage rates, and subsequent embryo quality were evaluated.
                Our results showed no statistically significant differences in fertilization rates, embryo cleavage rates, and quality of the embryos between the study group and the control group.
                Since the present study showed that long exposure of the oocyte to sperm has no advantage over short exposure, we prefer shortening the oocyte-sperm incubation period for reducing the negative effect induced by nonphysiologically high concentrations of spermatozoa. The potentially damaging effect of free O(2) radicals to cultured embryos may be reduced by adding scavengers to the culture media or by reducing the incubator O(2) levels. However, lowering the O(2) in the culture environment can be expensive, troublesome and may not be justifiable. The objective of this study was to evaluate the effect of lowered incubator O(2) tension on live birth rates in a predominately Day 5 embryo transfer program.
                Two hundred and thirty first-cycle women undergoing routine IVF or ICSI with ejaculated sperm were randomized in a prospective clinical trial and stratified for patient age and physician. Embryos of patients were randomly assigned for culture in either a 21% O(2) (atmospheric) or 5% O(2) (reduced) environment. Clinical endpoints monitored were rates of implantation, clinical pregnancy, live birth and blastocyst cryopreservation.
                Embryos cultured in a 5% O(2) environment consistently resulted in higher rates of live birth implantation (106/247, 42.9% versus 82/267, 30.7%; difference of 12.2% with 95% confidence interval (CI) of 3.9-20.3, P = 0.005) and live births (66/115, 57.4% versus 49/115, 42.6%; difference of 14.8% with 95% CI of 1.9-27.0, P = 0.043) when compared with rates among women whose embryos were cultured in an atmospheric O(2) environment.
                The overall increase in live births demonstrated by this study indicates that the effort and expense to culture embryos in a low-O(2) environment is justified. The study was registered at clinicaltrials.gov. NCT00708487. Ovulation induction alone, and ovulation induction in conjunction with one of four assisted procreation methods [intra-uterine insemination (IUI), intra-peritoneal insemination (IPI), gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization (IVF)] were tested as a treatment for male infertility in a prospective randomized trial. The trial when completed had generated data on 499 cycles from 346 patients. There was overwhelming evidence that some form of assisted procreation was beneficial, when compared to the spontaneous natural conception rate, which is generally assumed to be between 0.01 and 0.02 for male infertility. There was also firm evidence that IUI, GIFT or IVF (mean per cycle pregnancy rate 0.212) were superior to the remaining two treatments of IPI and ovulation induction alone (mean per cycle pregnancy rate 0.068). Duration of infertility and a diagnosis of endometriosis were the most important (adverse) pre-treatment factors detected. To investigate the effectiveness of double IUI and to determine the optimal timing of IUI in relation to hCG administration.
                Prospective randomized study.
                Infertility Center, Department of Obstetrics and Gynecology, University of Milan.
                Patients with male factor and unexplained infertility undergoing controlled ovarian hyperstimulation (COH) and IUI.
                After COH with clomiphene citrate and gonadotropins, patients were randomly assigned to one of the following groups: group A received a single IUI 34 hours after hCG administration, group B received a double IUI 12 hours and 34 hours after hCG administration, and group C received a double IUI 34 hours and 60 hours after hCG administration.
                Number of follicles > 15 mm in diameter on the day of hCG administration, number of motile spermatozoa inseminated, clinical pregnancy rate.
                Two hundred seventy-three patients underwent 449 treatment cycles: 90 patients were treated for 156 cycles in group A, 92 patients for 144 cycles in group B, and 91 patients for 149 cycles in group C. The overall pregnancies rates for groups A, B, and C were 13 (14.4% per patient and 8.3% per cycle), 28 (30.4% per patient and 19.4% per cycle), and 10 (10.9% per patient and 6.7% per cycle), respectively. There was a statistically significant difference between group B and groups A and C.
                Our data indicate that two IUIs performed 12 hours and 34 hours after hCG administration is the most cost-effective regimen for women undergoing COH cycles with clomiphene citrate and gonadotropins. Although the second insemination adds up to a slightly higher cost, it significantly increases the chance of pregnancy. To compare the results of fallopian tube sperm perfusion (FSP) versus standard intrauterine insemination (IUI) in patients with unexplained infertility undergoing controlled ovarian hyperstimulation (COH).
                Randomized, prospective, cross-over study.
                Reproductive medicine unit of a university hospital.
                Fifty-six couples with unexplained infertility.
                COH was induced by recombinant FSH and monitored by serial transvaginal ultrasound. On the day of hCG administration during the first treatment cycle, patients were randomized to either IUI or FSP. Thereafter, in case no pregnancy was achieved, patients went on being treated with FSP and IUI in alternate cycles. A maximum of four treatment cycles per couple was performed. FSP was performed using a pediatric Foley's catheter inseminating 4 mL of sperm-enriched suspension; a Kremer-Delafontaine catheter delivering 0.5 mL of sperm suspension was used for IUI.
                Clinical pregnancy rate per cycle.
                One hundred twenty-seven cycles (58 FSP, 69 IUI) were performed. The clinical pregnancy rate per cycle was 21.7% for IUI and 8.6% for FSP, respectively. No major adverse effects were recorded for either technique.
                After COH, FSP is less effective than IUI in couples with unexplained infertility.
This review has provided evidence that brief co-incubation of sperm and oocytes may improve the ongoing pregnancy and clinical pregnancy rates for infertile women undergoing IVF cycles. More RCTs are required to assess whether brief co-incubation would contribute to a higher live birth rate and a lower miscarriage rate compared to the standard overnight insemination protocol.