Assisted reproductive technologies (ARTs): evaluation of evidence to support public policy development.
ABSTRACT: Over the years, IVF/ICSI protocols have continued to evolve with efforts to improve outcomes. As a result, treatment success may be related to certain procedural factors, including number of embryos transferred and stage at which they are transferred. This review aims to assess the safety and effectiveness of IVF/ICSI in comparison to spontaneous conception and less invasive ARTs and the impact of procedure-related factors on the outcomes of IVF/ICSI in order to support the development of local clinical and policy guidance. Following Cochrane Collaboration guidelines and the PRISMA statement, a comprehensive systematic review of literature examining the impact of procedural characteristics on the safety or effectiveness of IVF/ICSI from 2007 to date was performed. 33 systematic reviews and 3 primary studies evaluating the impact of procedural differences, IVF/ICSI in comparison to less invasive ARTs, and ARTs in comparison to spontaneous conception were found. IVF was shown to offer significant benefits over no treatment and IUI in achieving pregnancy and live birth among couples with endometriosis or unexplained infertility. Frozen and blastocyst-stage embryo transfers were as effective as fresh and cleavage-stage embryo transfers, respectively. In comparison to single embryo transfer, double embryo transfer significantly increased pregnancy, live birth and multiple pregnancy/birth rates. IVF/ICSI was associated with more complications during pregnancy and delivery, and in infants compared to naturally conceived pregnancies, particularly when multiple embryo transfer was used. Frozen embryo transfer had fewer adverse events during pregnancy and delivery than fresh embryo transfer, and was at least as safe in terms of infant outcomes. The potential complications of IVF/ICSI may be minimized through procedural choices, but such choices often impact effectiveness. Thus, in developing clinical and policy guidance around IVF/ICSI, the risk-benefit trade-offs patients and providers are willing to accept must be carefully considered.
Project description:Great advances have been made in the field of assisted reproductive technology (ART) since the first in vitro fertilization (IVF) baby was born in Korea in the year of 1985. However, it deserve to say that the invaluable data from fertility centers may serve as a useful source to find out which factors affect successful IVF outcome and to offer applicable information to infertile patients and fertility clinics. This article intended to report the status of ART in 2009 Korean Society of Obstetrics and Gynecology surveyed. The current survey was performed to assess the status and success rate of ART performed in Korea, between January 1 and December 31, 2009. Reporting forms had been sent out to IVF centers via e-mail, and collected by e-mail as well in 2012. With International Committee Monitoring Assisted Reproductive Technologies recommendation, intracytoplasmic sperm injection (ICSI) and non-ICSI cases have been categorized and also IVF-ET cases involving frozen embryo replacement have been surveyed separately. Seventy-four centers have reported the treatment cycles initiated in the year of 2009, and had performed a total of 27,947 cycles of ART treatments. Among a total of 27,947 treatment cycles, IVF and ICSI cases added up to 22,049 (78.9%), with 45.3% IVF without ICSI and 54.7% IVF with ICSI, respectively. Among the IVF and ICSI patients, patients confirmed to have achieved clinical pregnancy was 28.8% per cycle with oocyte retrieval, and 30.9% per cycle with embryo transfer. The most common number of embryos transferred in 2009 is three embryos (40.4%), followed by 2 embryos (28.4%) and a single embryo transferred (13.6%). Among IVF and ICSI cycles that resulted in multiple live births, twin pregnancy rate was 45.3% and triple pregnancy rate was 1.1%. A total of 191 cases of oocyte donation had been performed to result in 25.0% of live birth rate. Meanwhile, a total of 5,619 cases of frozen embryo replacement had been performed with 33.7% of clinical pregnancy rate per cycle with embryo transfer. When comparing with international registry data, clinical pregnancy rate per transfer from fresh IVF cycles including ICSI (34.1%,) was comparable to clinical pregnancy rate per transfer in European Society for Human Reproduction and Embryology report was 32.5% though lower than 45.0% for USA data. There was no remarkable difference in status of assisted reproductive technology in Korea between the current report and the data reported in 2008. The age of women trying to get pregnant was reconfirmed to be the most important factor that may have impact on success of ART treatment.
Project description:BACKGROUND: Fertility treatment is associated with increased risk of major birth defects, which varies between in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), and is significantly reduced by embryo freezing. We therefore examined a range of additional perinatal outcomes for these exposures. METHODS: All patients in South Australia receiving assisted conception between Jan 1986-Dec 2002 were linked to the state-wide perinatal collection (all births/stillbirths ?20 weeks gestation or 400 g birth weight, n?=?306 995). We examined stillbirth, mean birth weight, low birth weight (<2500 g, <1500 g), small size for gestational age (<10th percentile, <3rd percentile), large size for gestational age (>90th percentile), preterm birth (32-<37 weeks, <32 weeks gestation), postterm birth (?41 weeks gestation), Apgar <7 at 5 minutes and neonatal death. RESULTS: Relative to spontaneous conceptions, singletons from assisted conception were more likely to be stillborn (OR?=?1.82, 95% Confidence Interval (CI) 1.34-2.48), while survivors as a group were comprehensively disadvantaged at birth, including lower birth weight (-109 g, CI -129--89), very low birth weight (OR?=?2.74, CI 2.19-3.43), very preterm birth (OR?=?2.30, CI 1.82-2.90) and neonatal death (OR?=?2.04, CI 1.27-3.26). Outcomes varied by type of assisted conception. Very low and low birth weight, very preterm and preterm birth, and neonatal death were markedly more common in singleton births from IVF and to a lesser degree, in births from ICSI. Using frozen-embryos eliminated all significant adverse outcomes associated with ICSI but not with IVF. However, frozen-embryo cycles were also associated with increased risk of macrosomia for IVF and ICSI singletons (OR?=?1.36, CI 1.02-1.82; OR?=?1.55, CI 1.05-2.28). Infertility status without treatment was also associated with adverse outcomes. CONCLUSIONS: Births after assisted conception show an extensive range of compromised outcomes that vary by treatment modality, that are substantially reduced after embryo freezing, but which co-occur with an increased risk of macrosomia.
Project description:Objective: This study aimed to investigate the associations between previous TORCH infection (cytomegalovirus, toxoplasmosis, herpes simplex virus, and rubella) with pregnancy and neonatal outcomes in couples undergoing IVF/ICSI-ET. Materials and Methods: A total of 18,074 couples underwent fresh IVF/ICSI-ET (in vitro fertilization/intracytoplasmic sperm injection-embryo transfer) cycles were included in our analyses. TORCH infection status was determined by serological confirmation of cytomegalovirus, toxoplasmosis, herpes simplex virus, and rubella IgG in the absence of IgM antibodies. Clinical pregnancy, ectopic pregnancy, miscarriage, live birth, preterm birth, congenital malformation, and perinatal death were evaluated in both infection and non-infection group. Multivariate logistic regression was applied to calculate odds ratio. Results: Previous toxoplasmosis infection is associated with a significantly decreased preterm birth rate [P = 0.045, OR = 0.755 (95% CI, 0.571-0.997), Adjusted OR = 0.749 (95%CI, 0.566-0.991)]. No differences in clinical pregnancy, ectopic pregnancy, miscarriage, and perinatal death were observed between the corresponding TORCH infection group [IgM (-) IgG(+)] and the non-infection group [IgM (-) IgG (-)]. Conclusions: Previous TORCH infections were not associated with adverse pregnancy and neonatal outcomes in IVF/ICSI-ET overall, and toxoplasmosis infection might be associated with a lower preterm birth rate in patients underwent IVF/ICSI-ET. The necessity of TORCH IgG screening in IVF procedure might need re-evaluation, and further cost-effective analysis might be helpful for the clinical management strategy.
Project description:Sperm morphology is the best predictor of fertilization potential, and the critical predictive information for supporting assisted reproductive methods selection. Given its important predictive value and the declining reality of semen quality in recent years, the threshold of normal sperm morphology rate (NSMR) is being constantly corrected and controversial, from the 4th edition (14%) to the 5th version (4%). We retrospectively analyzed 4756 cases of infertility patients treated with conventional-IVF(c-IVF) or ICSI, which were divided into three groups according to NSMR: ?14%, 4%-14% and <4%. Here, we demonstrate that, with decrease in NSMR(?14%, 4%-14%, <4%), in the c-IVF group, the rate of fertilization, normal fertilization, high-quality embryo, multi-pregnancy and birth weight of twins gradually decreased significantly (P<0.05), while the miscarriage rate was significantly increased (p<0.01) and implantation rate, clinical pregnancy rate, ectopic pregnancy rate, preterm birth rate, live birth rate, sex ratio, and birth weight(Singleton) showed no significant change. In the ICSI group, with decrease in NSMR (?14%, 4%-14%, <4%), high-quality embryo rate, multi-pregnancy rate and birth weight of twins were gradually decreased significantly (p<0.05), while other parameters had no significant difference. Considering the clinical assisted methods selection, in the NFMR ?14% group, normal fertilization rate of c-IVF was significantly higher than the ICSI group (P<0.05), in the 4%-14% group, birth weight (twins) of c-IVF were significantly higher than the ICSI group, in the <4% group, miscarriage of IVF was significantly higher than the ICSI group. Therefore, we conclude that NSMR is positively related to embryo reproductive potential, and when NSMR<4% (5th edition), ICSI should be considered first, while the NSMR?4%, c-IVF assisted reproduction might be preferred.
Project description:Aims: To determine the impact of advanced endometriosis (EMS) on in vitro fertilization/intracytoplasmic sperm injection and frozen-thawed embryo transfer (IVF/ICSI-FET) outcomes and analyze the influencing factors. Methods: A retrospective study was conducted on sterile women with ovarian endometriomas (OMAs), including patients who underwent laparoscopic cystectomy (n = 224, 224 IVF/ICSI cycles, 205 FET cycles) and aspiration (n = 139, 139 IVF/ICSI cycles, 148 FET cycles); peritoneal EMS (n = 96, 96 IVF/ICSI cycles, 89 FET cycles); and tubal factors (n = 360, 360 IVF/ICSI cycles, 474 FET cycles). Our main outcomes included the number of MII oocytes retrieved, fertilization rate, the number of viable embryos, viable embryo rate per oocyte retrieved in oocyte retrieval cycles, and clinical pregnancy rate per transfer, live birth rate per transfer, and cumulative clinical pregnancy rate of this oocyte retrieval cycle in FET cycles. Finally, binary logistic regression analysis was performed to generate a prediction model for cumulative clinical pregnancy. Results: The results showed that significantly fewer MII oocytes retrieved and viable embryos and lower viable embryo rate and cumulative clinical pregnancy rate were observed in women with EMS compared with the control. Women with peritoneal EMS had lower fertilization rate and viable embryo rate per oocyte retrieved than patients with OMA (all p < 0.05). However, the pregnancy outcomes were not significantly different between the two phenotypes. The patients who underwent laparoscopic cystectomy had fewer MII oocytes retrieved and viable embryos compared with those with intact endometrioma(s) but no significant difference in pregnancy outcomes between the two types of OMA patients. By binary logistic regression analysis, antral follicle count (AFC) was found to be an independent factor associated with cumulative clinical pregnancy in this oocyte retrieval cycle (odds ratio = 1.054; 95% confidence interval, 1.011-1.100; p = 0.014), and the AFC prediction model of cumulative clinical pregnancy was established, with an area under the curve of 0.60. Conclusions: Our data supported that advanced EMS has negative effect on cumulative clinical pregnancy per oocyte retrieval cycle, and AFC is an independent predictor, which is mainly caused by poor ovarian response associated with OMA per se or its surgery and the damage of peritoneal EMS to oocyte maturation.
Project description:INTRODUCTION:Endometrial trauma commonly known as endometrial scratch (ES) has been shown to improve pregnancy rates in women with a history of repeated implantation failure undergoing in vitro fertilisation (IVF), with or without intracytoplasmic sperm injection (ICSI). However, the procedure has not yet been fully explored in women having IVF/ICSI for the first time. This study aims to examine the effect of performing an ES in the mid-luteal phase prior to a first-time IVF/ICSI cycle on the chances of achieving a clinical pregnancy and live birth. If ES can influence this success rate, there would be a significant cost saving to the National Health Service through decreasing the number of IVF/ICSI cycles necessary to achieve a pregnancy, increase the practice of single embryo transfer and consequently have a large impact on risks and costs associated with multiple pregnancies. METHODS AND ANALYSIS:This 30-month, UK, multicentre, parallel group, randomised controlled trial includes a 9-month internal pilot and health economic analysis recruiting 1044 women from 16 fertility units. It will follow up participants to identify if IVF/ICSI has been successful and live birth has occurred up to 6 weeks post partum. Primary analysis will be on an intention-to-treat basis. A substudy of endometrial samples obtained during the ES will assess the role of immune factors in embryo implantation. Main trial recruitment commenced on January 2017 and is ongoing.Participants randomised to the intervention group will receive the ES procedure in the mid-luteal phase of the preceding cycle prior to first-time IVF/ICSI treatment versus usual IVF/ICSI treatment in the control group, with 1:1 randomisation. The primary outcome is live birth rate after completed 24 weeks gestation. ETHICS AND DISSEMINATION:South Central-Berkshire Research Ethics Committee approved the protocol. Findings will be submitted to peer-reviewed journals and abstracts to relevant national and international conferences. TRIAL REGISTRATION NUMBER:ISRCTN23800982; Pre-results.
Project description:BACKGROUND:This study focused on the outcomes of patients with pericentric inversion of chromosome 9 who underwent IVF/ICSI and fresh day 2 or day 3 embryo transfer and the possible impacts of carrier gender and chromosome karyotype on pregnancy outcomes. METHODS:A total of 214 couples (107 couples with one pericentric inversion of chromosome 9 in one partner [Group 1], 107 couples with normal karyotypes [Group 2]) underwent their first IVF/ICSI treatment and were included in this study. Oocyte number, normal fertilization rates, abnormal fertilization rates, cleavage rates, embryo utilization rates, fresh embryo transfer rates, clinical pregnancy rates (CPR), implantation rates, miscarriage rates, and live birth rates per embryo transfer (LBR) were compared between groups. RESULTS:Group 1 did not show any disadvantage when compared with Group 2. The CPR and LBR were similar between all groups. The female carrier group had a higher normal fertilization rate and higher utilization rate than the male carrier group. Cases with inv(9)(p12;q13) had a lower utilization rate but a higher implantation rate than the remaining karyotypes. CONCLUSION:In the first IVF or ICSI cycle, couples with one pericentric inversion of chromosome 9 in one partner had satisfactory outcomes. The subgroup analysis showed a tendency of better prognosis for the female carrier and inv(9)(p12;q13) type.
Project description:This study compared the cumulative live birth rates following Intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilization (cIVF) in women aged 40 years or more and unexplained infertility. A cohort of 685 women undergoing either autologous conventional IVF or ICSI was retrospectively analyzed. The effects of conventional IVF or ICSI procedure on cumulative pregnancy and live birth rates were evaluated in univariate and in multivariable analysis. In order to reduce potential differences between women undergoing either IVF or ICSI and to obtain unbiased estimation of the treatment effect, propensity score was estimated. ICSI was performed in 307 couples (ICSI group), whereas cIVF was performed in 297 couples (cIVF group), resulting in 45 and 43 live deliveries, respectively. No differences were observed in morphological embryo quality, in the number of cleavage stage embryos, in the number of transferred embryos, and in the number of vitrified embryos. As for the clinical outcome, no differences were observed in pregnancy rate, cumulative pregnancy rate, live birth rate, cumulative live birth rate, and abortion rate. The present results suggest that ICSI is not associated with increased likelihood of a live birth for unexplained, non-male factor infertility, in women aged 40 years or more.
Project description:Importance:Metformin is widely used among women with polycystic ovary syndrome (PCOS). However, its associations with outcomes of in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in women with PCOS remain controversial. Objective:To assess whether metformin is associated with improved outcomes of IVF/ICSI-ET in women with PCOS. Data Sources:PubMed, Embase, and Cochrane were searched from database inception to January 31, 2020. Study Selection:Only randomized clinical trials (RCTs) were included. Eligible studies enrolled women with PCOS undergoing infertility treatment with IVF/ICSI-ET and reported at least 1 outcome of IVF/ICSI-ET. Data Extraction and Synthesis:This study followed the Preferred Reporting Items for Systematic Reviews and Meta analyses guidelines. Two authors independently extracted the data. Study quality was evaluated using the GRADE system. Treatment effect was quantified using odds ratios (ORs) with 95% CIs using random-effect models with the Mantel-Haenszel method. Main Outcomes and Measures:Ovarian hyperstimulation syndrome (OHSS), clinical pregnancy rate, and live birth rate. Results:A total of 12 RCTs, which collectively included 1123 women with PCOS undergoing infertility treatment with IVF/ICSI-ET, were identified. The risk of OHSS in women randomized to metformin was lower than in women not randomized to metformin (OR, 0.43; 95% CI, 0.24-0.78), although this difference was not significant for women with PCOS with a body mass index of less than 26 (OR, 0.67; 95% CI, 0.30-1.51). There was no significant difference in clinical pregnancy rate (OR, 1.24; 95% CI, 0.82-1.86) or live birth rate (OR, 1.23; 95% CI, 0.74-2.04) in the total population studied. However, in a post hoc analysis among women with a body mass index of 26 or greater, metformin treatment was associated with increased clinical pregnancy rates (OR, 1.71; 95% CI, 1.12-2.60). Conclusions and Relevance:In this study, metformin treatment was associated with a decreased risk of OHSS but had no association with the overall clinical pregnancy rate or live birth rate among women with PCOS undergoing IVF/ICSI-ET. Metformin treatment should be carefully considered for women with PCOS undergoing IVF/ICSI-ET and may be more preferred for women with a body mass index greater than 26.
Project description:Introduction: Although pre-treatment with a GnRH agonist can reduce the size of adenomyosis lesions, the supra-physiological hormone level induced by controlled ovarian hyperstimulation (COH) may negate the usefulness of the GnRH agonist in patients with adenomyosis lesions, leading to continued poor outcomes in fresh embryo transfer cycles during in vitro fertilization (IVF). It is unclear whether GnRH agonist pre-treatment before starting the long GnRH agonist protocol for IVF/ICSI (intracytoplasmic sperm injection) can improve cumulative live birth rate (CLBR) of infertile women with adenomyosis.Method: In this retrospective cohort study, a total of 374 patients diagnosed as adenomyosis (477 cycles) underwent IVF/ICSI with long GnRH agonist protocol with or without GnRH agonist pre-treatment between January 2009 and June 2018. Logistic regression was used to assess the association between GnRH agonist pre-treatment and pregnancy outcome after adjusting for confounding factors.Results: The live birth rate in fresh embryo transfer cycles was higher in the non-pre-treatment group than in the GnRH agonist pre-treatment group (37.7 vs. 21.2%, P = 0.028); the adjusted odds ratio (OR) for the long agonist protocol without pre-treatment was 1.966 (95% CI: 0.9–4.296, P = 0.09). The CLBR was higher in the non-pre-treatment group than in the GnRH agonist pre-treatment group (40.50 vs. 27.90%, P = 0.019); the adjusted OR for the long agonist protocol without pre-treatment was 1.361 (95% CI: 0.802–2.309, P = 0.254).Conclusion: Our results indicated that GnRH agonist pre-treatment before starting the long GnRH agonist protocol does not improve the live birth rate in fresh embryo transfer cycles or CLBR in infertile women with adenomyosis after IVF/ICSI treatment when compared to that in non-pre-treated patients. A subsequent prospective randomized controlled study is needed to confirm these results.