A randomized double-blind controlled study of the efficacy of laser-assisted hatching on implantation and pregnancy rates of frozen-thawed embryo transfer at the cleavage stage. Assisted hatching does not enhance IVF success in good-prognosis patients. Does assisted hatching improve implantation rates after in vitro fertilization or intracytoplasmic sperm injection in all patients? A prospective randomized study. Impact of assisted hatching on fresh and frozen-thawed embryo transfer cycles: a prospective, randomized study. A prospective, randomized, double-blind study for the evaluation of assisted hatching in patients with advanced maternal age. Laser assisted hatching in good prognosis patients undergoing in vitro fertilization-embryo transfer: a randomized controlled trial. Laser-assisted hatching increases pregnancy and implantation rates in cryopreserved embryos that were allowed to cleave in vitro after thawing: a prospective randomized study. A European multicentre prospective randomized study to assess the use of assisted hatching with a diode laser and the benefit of an immunosuppressive/antibiotic treatment in different patient populations. A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program.
Assisted hatching (AH) in fresh embryo transfer (ET) cycles increases the implantation and pregnancy rates, especially in women with a poor prognosis, repeated implantation failures and in older women. Little information exists in the literature regarding the role of AH in frozen-thawed embryo transfer (FET) cycles.
                Embryos were cryopreserved at the cleavage stage. On the day of FET, 160 patients were randomized according to a computer-generated randomization list in sealed envelopes into the AH group and the control group. The patients and the clinicians were blinded to the group assigned. In the AH group, the outer half of the zona pellucida over a quarter of the diameter of zona was removed using a 1480 nm non-contact laser.
                The two groups were comparable in terms of demographic characteristics, ovarian response of the stimulated cycle and quality of fresh and frozen-thawed embryos. No differences in implantation, pregnancy and multiple pregnancy rates were found between the two groups. There was a non-significant trend of a higher implantation rate in the AH group when the zona thickness was > or = 16 mm.
                Laser AH did not improve the implantation rate of FET cycles and should not be performed routinely in all frozen-thawed embryos at the cleavage stage. The role of assisted hatching in good-prognosis IVF patients was evaluated in a prospective, randomized, controlled pilot study, which was followed by a retrospective observational series.
                After assisted hatching was proved successful in a mouse embryo study, 20 good-prognosis IVF patients were randomly assigned to either assisted hatching (13) or no assisted hatching (7; the controls). Following this series, 27 good-prognosis IVF patients were retrospectively evaluated to determine the outcome with assisted hatching.
                In the prospective study, clinical pregnancies resulted from 3 (23%) of 13 patients in the hatching group, compared to 3 (43%) of 7 in the control group. Implantation rates were similar: 9.6% in the hatching group and 10.7% in the controls. In the retrospective series, the 11.1% implantation rate with assisted hatching was significantly less than the 42.9% implantation rate seen with traditional IVF.
                Implantation and pregnancy rates are high in young women undergoing traditional IVF. Assisted hatching is not beneficial in these patients. Preliminary data from some research centers indicate that assisted hatching might be of value to increase embryo implantation rate in the human, at least in selected cases. It is not clear, however, whether this technique would be of benefit for all patients undergoing an embryo transfer. We therefore performed a prospective randomized study to evaluate the effect of assisted hatching on the implantation rate in our in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) program.
                In total, 120 couples undergoing an embryo transfer were randomized between two groups: in one group no assisted hatching was performed (AH-), whereas in the other group the embryos selected for transfer were subjected to partial zona dissection (PZD) immediately prior to the transfer (AH+). Using a computer-generated minimization procedure, patients were allocated to one of the two groups according to four pre-selected criteria: the number of embryos transferred, the cumulative score of transferred embryos, the age of the patient, and the use of ICSI.
                Pregnancy and implantation rates in the AH+ and AH- groups were, respectively, 42.1 versus 38.1% and 17.9 versus 17.1%.
                From our data we conclude that assisted hatching through partial zona dissection prior to embryo transfer does not improve pregnancy and embryo implantation rates in unselected patients undergoing IVF or ICSI. The aim of this study was to determine if assisted hatching (AH) could improve the rates of pregnancy and implantation for both fresh and frozen-thawed embryo transfer cycles. A total of 760 fresh embryo transfer cycles and 200 frozen-thawed embryo transfer cycles were randomly assigned to either the treatment group (AH) or the control group (no AH). Zona thinning by laser was performed just before embryo transfer. In fresh embryo transfer cycles, the AH group and control group results were comparable. There were no significant differences in the rates of positive human chorionic gonadotrophin (HCG; 47.5 versus 48.8%), clinical pregnancy (42.4 versus 42.6%), or implantation (26.3 versus 25.2%) between the two groups. However, in frozen-thawed embryo transfer cycles, the rates of positive HCG (32.0 versus 17.0%), clinical pregnancy (25.0 versus 14.0%) and implantation (16.7 versus 7.3%) were significantly greater in the AH group than in the control group (P &lt: 0.05). The results of this investigation show that in the fresh embryo transfer cycles, laser-assisted hatching by zona thinning has no impact on the rates of positive HCG, clinical pregnancy and implantation, whereas in frozen-thawed cycles, assisted hatching by zona thinning significantly increases all three of these rates. The objective of this study was to determine if assisted hatching improved the rates of implantation, clinical pregnancy and ongoing pregnancy for in-vitro fertilization (IVF) patients aged > or =36 years. On the day of oocyte aspiration, consenting patients were randomized according to whether all embryos underwent the hatching procedure (hatched; n = 41) or all embryos remained unhatched (controls; n = 48). Patients in both groups were treated with methylprednisolone and doxycycline starting on the day of oocyte retrieval and continuing for 4 days. The hatching procedure was performed approximately 55 h after insemination on all potential embryos for transfer and employed the release of acidified acid Tyrode's medium against the zona pellucida to create an opening approximately 20 microm in diameter. No significant differences were noted in the mean age, number of oocytes aspirated and number of embryos transferred between the hatched and control groups. In addition, no significant differences were observed in the rates of implantation (11.1 versus 11.3%), clinical pregnancy (39.0 versus 41.7%) and ongoing pregnancy (29.3 versus 35.4%) between the hatched and control groups respectively. These results suggest that assisted hatching may have no significant impact on IVF success rates in the patient population studied. To evaluate whether assisted hatching improves clinical outcomes of embryo transfers to good prognosis patients, defined as patients < or =39 years with normal follicle-stimulating hormone (FSH) and E(2) levels, no more than one previous unsuccessful cycle of in vitro fertilization (IVF)-embryo transfer, and good embryo quality.
                Prospective randomized controlled trial.
                Private assisted reproductive technology (ART) center.
                One hundred ninety-nine good prognosis patients undergoing IVF-embryo transfer.
                In vitro fertilization followed by embryo transfer on day 3 after oocyte retrieval with or without assisted hatching using a 1,480-nm wavelength infrared laser.
                Clinical intrauterine pregnancy, spontaneous pregnancy loss, and live birth.
                Rates of clinical intrauterine pregnancy with fetal cardiac activity (53% vs. 54% per cycle), spontaneous pregnancy loss (13% vs. 16% per pregnancy), and live birth (47% vs. 46% per cycle) were very similar between treatment cycles with laser-assisted hatching and control cycles in which embryos were transferred without assisted hatching. There were no significant differences between treatment and control groups in any measured clinical outcome parameters.
                Assisted hatching does not improve clinical outcomes among good prognosis patients. Cryopreservation of embryos may lead to zona hardening that may compromise in vivo hatching and implantation following thawing and transfer. Assisted hatching (AH) has been advocated as a means of assisting the natural hatching process and enhancing implantation.
                The aim of this study was to assess in a prospective randomized manner the effect of laser-assisted hatching (LAH) on implantation as well as clinical and multiple pregnancy rates (the primary outcome) after the transfer of frozen-thawed embryos. All embryos were thawed the day before transfer, and LAH was performed the next day on embryos that cleaved. Control group consisted of embryos that were transferred without AH.
                The performance of LAH significantly increased implantation (9.9 versus 20.1%, P < 0.01), clinical pregnancy (27.3 versus 40.9, P < 0.05) and multiple pregnancy rates (16 versus 40.3%, P < 0.07). In the LAH group, significantly more excess embryos that were left in culture hatched in vitro.
                LAH improves the outcome of frozen-thawed embryo transfer when performed before transfer on embryos that were allowed to cleave. Assisted hatching (AH) techniques, designed for facilitating the embryo escape out of the zona pellucida (ZP) have been used in IVF centres since 1992. The initial indications for AH were patient's age, ZP thickness, high basal FSH and repeated IVF failures. Several retrospective and prospective studies assessing AH in these indications have given disparate results. Our aims were to evaluate the benefits of AH and immunosuppressive/antibiotic treatment (IA) in patients with either a poor prognosis of success, previous implantation failures or transfers of cryopreserved embryos.
                Four IVF centres allocated 426 patients, randomized for AH and IA, into four groups of AH indications between 1997 and 1999. AH was performed with a diode laser. ZP thickness, opening size and embryo score were recorded. Outcome measures were implantation and delivery rates.
                Patients coming for a first or third transfer of cryopreserved embryos and poor prognosis patients admitted for a first trial did not benefit from AH. Even patients with repeated implantation failures of fresh embryos did not gain significantly from AH.
                Among AH indications, absence of implantation after several transfers of good quality embryos remains the strongest patient selection criterion. Prescription of an immunosuppressive/antibiotic treatment is essential. 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.
This update has demonstrated that whilst assisted hatching (AH) does appear to offer a significantly increased chance of achieving a clinical pregnancy, the extent to which it may do so only just reaches statistical significance. The 'take home' baby rate was still not proven to be increased by AH. The included trials provided insufficient data to investigate the impact of AH on several important outcomes. Most trials still failed to report on live birth rates.