Is elective single embryo transfer a cost-effective alternative to double embryo transfer?

Elective single embryo transfer (eSET) is increasingly being considered as a means to reduce twin pregnancies associated with in vitro fertilisation treatment. However, it is important to consider the cost-effectiveness of alternative strategies when considering a change in policy. A review of the literature showed only five studies assessing both costs and consequences of strategies involving eSET compared with double embryo transfer. Several limitations in these studies prevent a definitive conclusion on the cost-effectiveness of eSET being reached. Future economic evaluations need to compare strategies relevant to routine practice, include all relevant costs, measure and value longer term outcomes appropriately, and assess the cost-effectiveness of eSET across different subgroups of women.     

Computer-assisted embryo selection: a benefit in the evaluation of embryo quality?

Embryo selection is based on embryo developmental and morphological characteristics. Standard embryo evaluation has some disadvantages. New technology using multilevel images combined with a computer-assisted scoring system (CASS) has the potential to overcome these disadvantages. The aim of this study was to compare the value of a computer-assisted scoring system (CASS) versus a standard scoring system (SSS) in predicting implantation and live birth. This prospective study included 3185 embryos obtained during 502 IVF/intracytoplasmic sperm injection cycles with single-embryo transfer on day 3. Embryos were evaluated with two scoring systems: SSS and CASS. Logistic regression analyses were performed using implantation and live birth as outcomes. According to multiple regression analysis, implantation was influenced by number and size of blastomeres on day 3 using CASS and by all embryo parameters on day 3 using SSS. Combined analysis of both scoring systems revealed that implantation was affected by number and size of blastomeres using CASS and by the degree of embryo fragmentation using SSS. Using live birth as outcome, only the number of blastomeres on day 3, evaluated by SSS and CASS, was predictive. Prediction of implantation and live birth may be superior using CASS when compared with SSS.Embryo selection is currently based on embryo developmental and morphological characteristics of an embryo using a standard scoring system. This evaluation system is limited by a number of disadvantages. New technology using multilevel images combined with a computer-assisted scoring system has the potential to overcome these disadvantages. The aim of this study was to compare the value of such computer-assisted scoring system versus a standard scoring system in predicting implantation and live birth rate. This study included 3185 embryos obtained during 502 IVF or intracytoplasmic sperm injection cycles with single-embryo transfer on day 3. All the embryos were evaluated with two types of scoring systems: a standard scoring system and a computer-assisted scoring system. According to the statistical analysis, the implantation of an embryo was influenced by the number and size of blastomeres on day 3 when evaluated with the computer-assisted scoring system, and by all embryo parameters on day 3 using the standard scoring system. Combined analysis of both scoring systems revealed that implantation was affected by number and size of blastomeres using the computer-assisted scoring system and by the degree of embryo fragmentation using the standard scoring system. Live birth was influenced by the number of blastomeres on day 3 evaluated by both scoring systems. Prediction of embryo implantation and live birth was superior using the computer-assisted scoring system. In conclusion, a computer-assisted scoring system may be superior to a standard scoring system in the prediction of implantation and live birth.     

Uterine receptivity and embryo–uterine interactions in embryo implantation: lessons from mice

Implantation is a process of the first feto-maternal encounter in the uterus. A competent blastocyst and a receptive uterus are critical for successful implantation. For an acquisition of uterine receptivity, the following conditions need to be satisfied in the uterine environments: the endometrial preparation with stromal proliferation and epithelial differentiation in the pre-receptive phase and proper interactions between the uterus and blastocyst later in the phase. Focusing on these points and primarily referring to the mouse in vivo evidence, this review article has shown detailed molecular mechanisms for successful implantation.     

Assessment of mammalian embryo quality: what can we learn from embryo morphology?

Embryo morphology assessment, however imperfect it may be, is at present the most popular method for embryo selection prior to transfer, both in human and bovine assisted reproduction. A major difference between human and bovine embryos is the fact that in the latter, assessment of morphology is jeopardized by the opacity of the blastomeres, which is caused by lipid droplet accumulation. This opacity makes it difficult to assess nuclear and nucleolar morphology, aspects which can easily be evaluated in human zygotes or early cleaving embryos. However, recent research which focused on correlation between bovine embryo morphology and embryonic ultrastructure, gene expression and cryoresistance, has provided evidence that much more can be deduced from mere embryo morphology than previously thought. Morphological features such as colour of the blastomeres, the extent of compaction, timing of blastocyst formation and expansion and diameter of the embryo at hatching can be linked with embryo quality. On the other hand, cattle embryos of deviant chromosomal constitution or with aberrant genetic make-up cannot be selected against by means of the current morphological techniques. Possible solutions include the visualization of bovine pronuclei at the zygote stage by means of ultracentrifugation or multiphoton laser scanning microscopy, and adjustment of genetic analysis in order to reconstruct embryo genetic make-up starting from the biopsy material.     

What does an embryo need?

This review argues that the question "What does an embryo need?" cannot be adequately answered in quantitative terms to allow the formulation of media for culturing early mammalian embryos. It can be shown experimentally that "needs" in terms of the nutrients an embryo chooses to consume, and their rates of consumption, vary widely, as they are determined by the concentration of the nutrients under consideration and other constituents in the culture medium. Similarly, it is impossible to define "needs" from knowledge of the kinetic properties of nutrient transport systems. Measurements of nutrient consumption, are, however, valuable in determining overall metabolic activity and the balance between oxidative and glycolytic metabolism, in demonstrating qualitative requirements for specific nutrients and in providing markers of normality or abnormality against which to devise methods for diagnosing embryo health. On the basis of these and other considerations, a strategy is proposed for the formulation of embryo culture media that promotes metabolism that is "quiet" rather than "active", reduces the concentrations of nutrients to match those in the Fallopian tube, selects the "quietest" embryos for transfer, and trusts the autonomy of the embryo.     

Does hyaluronan improve embryo implantation?

PURPOSE OF REVIEW: Taking into consideration the increasing interest on hyaluronan and its biological as well as physiological properties, this review will focus on the role of this molecule in human embryo implantation. RECENT FINDINGS: Several studies have been performed up to date in order to assess whether the addition of hyaluronan in the human embryo culture system can improve pregnancy and implantation rates, including one retrospective and six randomized controlled trials. On the one hand, four of those studies showed significant increase in clinical pregnancy and/or implantation rates after using embryo transfer medium containing high concentration of hyaluronan. On the other hand, three studies did not demonstrate any significant improvement in clinical pregnancy and implantation rates. However, regardless of statistical significance, almost all studies demonstrate higher pregnancy and implantation rates after using embryo transfer medium containing high concentration of hyaluronan. SUMMARY: Up to date, the results regarding the role of hyaluronan in human embryo implantation are still conflicting and, thus, further prospective randomized clinical trials are necessary to draw solid conclusions.     

How to improve ART results? Is France behind other countries? Strategy for single embryo transfer: The value of embryo selection and embryo freezing

Multiple embryo transfer is associated with a high frequency of twin pregnancies with costly complications involving both mother and child. As a result high priority is currently being given to the development of single embryo transfer (SET) programs. France seems to be lagging behind Northern European countries in the development of SET and widespread use of SET will depend on convincing physicians that this policy will not have a negative impact on success rate, as has been the case for many protocols described in the literature as well as in our own experience. Our SET program includes patients less than 36 years of age undergoing their first FIV-ICSI. If two embryos showing satisfactory morphology are obtained, one is selected transferred and the other is systematically frozen. Selection for transfer is based on two criteria, i.e. observation of even early cleavage 26 hours after FIV-ICSI and evaluation of embryo morphology score on day 2. Embryo morphology score is based on the presence of four blastomeres and absence of blastomere irregularities and anucleated fragmentation. Last, a prerequisite for SET is an effective freezing program. A pregnancy rate of 13% per thawing was sufficient enough to obtain a cumulative pregnancy rate after SET (N = 205) and subsequent frozen embryo transfer (FET) similar to the cumulative pregnancy rate obtained after double embryo transfer (N = 394) and subsequent FET (46.3 vs 46.7%, NS). Twin delivery rate were respectively 2,6% after SET and 26,6% after double embryo transfer (P < 0.01).     

Does sperm origin affect embryo morphokinetic parameters?

Purpose

The purpose of our study was to use time-lapse in order to evaluate the impact of sperm origin (fresh ejaculate or surgically retrieved) on embryo morphokinetic parameters and clinical outcome in intracytoplasmic sperm injection (ICSI) cycles.

Methods

This retrospective monocentric study was conducted in 485 unselected couples undergoing 604 ICSI cycles with embryo culture in the Embryoscope®. Among them, 445 couples underwent ICSI cycle with fresh ejaculated sperm and 40 with surgically retrieved sperm (26 with testicular sperm and 14 with epididymal sperm). Embryo morphokinetic parameters and clinical cycle outcome were compared between fresh ejaculated sperm and surgically retrieved sperm. A subgroup analysis was also conducted between testicular and epididymal sperm ICSI cycles.

Results

Clinical outcome was comparable between groups according to sperm origin. Although most early morphokinetic parameters were comparable between ejaculated and surgical sperm groups, a few parameters were significantly different between both groups, but with a considerable overlap in their distribution. Late cellular events occurred significantly later in the surgical sperm group than in the ejaculated sperm group.

Conclusions

Morphokinetic analysis did not allow us to identify clinically relevant differences between fresh ejaculate and surgically retrieved sperm groups. Further studies are needed, especially concerning the relationship between sperm origin and late morphokinetic parameters, such as blastocyst development.     

Controversies in clinical embryology: embryo selection towards single embryo transfer – 16 July 2008, University of Manchester

Quantitative researchers may argue that a finding or result is more likely to be accepted as a fact if it is quantified (expressed in numbers), than if it is not (Black, ). ‘There is little or no scientific evidence, for example to support the well-known “fact” that one couple in 10 is infertile, yet most of us are happy to accept uncritically such simplified, reductionist, and blatantly incorrect statements, so long as they contain at least one number’ (Greenhalgh & Taylor, , p. 740). Interest in qualitative methods and their wider exposure in health care has led to necessary scrutiny of this type of research (Mays & Pope, ). This article compares the basic purpose and focus of quantitative and qualitative research, and draws attention to the relative lack of qualitative research in fertility and reproduction compared to quantitative methods. The authors highlight the strengths and weaknesses of both methods and promote qualitative methods as a valuable tool in fertility and reproduction related studies.     

Does IVF cleavage stage embryo quality affect pregnancy complications and neonatal outcomes in singleton gestations after double embryo transfers?

Purposes

Embryo quality is associated with successful implantation and live births. Our retrospective study was carried out to determine whether or not cleavage stage embryo quality affects the miscarriage rate, pregnancy complications and neonatal outcomes of singletons conceived with assisted reproduction technology.

Method

The current study included 11,721 In Vitro Fertilization-Embryo Transfer cycles (IVF-ET) between January 2009 (the date at which electronic medical records were implemented at our center) and March 2013. Only women < 40 years of age undergoing their first fresh embryo transfer cycle using non-donor oocytes were included.

Results

Our study indicated that the transfer of poor-quality embryos resulted in higher miscarriage (19.77 % vs. 13.28 %, p = 0.02) and lower ongoing pregnancy rates (15.33 % vs. 48.06 %, p < 0.001). Logistic regression analysis performed on data derived from 744 cycles culminating in miscarriages versus 4,333 cycles culminating in live births, suggested that embryo quality (p = 0.04) is significantly associated with miscarriage rate after adjusting for other confounding factors. Moreover, there were no differences in the mean birth weight, low birth weight (<2,500 g), very low birth weight (<1,500 g), gestational age, preterm delivery (<37 weeks), very preterm delivery (<32 weeks), congenital malformations, small-for-gestational-age singletons (SGA), and large-for-gestational-age singleton (LGA) rate (p > 0.05). Similarly, pregnancy complications resulting from poor-quality embryos were not different from good-quality embryos (4.04 % vs. 2.57 %, p = 0.33). Finally, logistic regression suggested that embryo quality was not significantly associated with pregnancy complications after adjusting for other confounding factors (p = 0.40).

Conclusions

Our study suggests that transfer of poor-quality embryos did not increase the risk of adverse outcomes; however, the quality of cleavage stage embryos significantly affected the miscarriage rate and ongoing pregnancies.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-014-0351-8) contains supplementary material, which is available to authorized users.     

Consecutive cycles in in vitro fertilization–embryo transfer

Background.?The decline of female fertility with advancing age is well documented. The aim of this study was to compare the ovarian performance after repeated ovarian stimulation cycles in women of different ages.

Methods.?Four hundred patients who started at least three in vitro fertilization (IVF) cycles during the 5-year period between 1998 and 2002 were identified. The patients were divided into four groups: the 25–30 age group (n?=?90), the 31–35 age group (n?=?150), the 36–40 age group (n?=?110) and the 41–45 age group (n?=?50).

Results.?Comparing subsequent cycles versus the first treatment cycle we found a statistically significantly increased number of ampules of recombinant follicle stimulating hormone (rFSH) needed to reach follicles maturation (p?<?0.001). The number of ampules of gonadotropin required was significantly higher (p?<?0.001) in the groups of advanced age compared with the groups of young women. For women in the 36–40 group and in the 41–45 group we found the number of follicles, the number of oocytes and the proportion of grade A embryos, in every cycle, were significantly lower than in the groups of young women. We compared the characteristics of ovarian stimulation and response of a single age group in different consecutive cycles. We found significant differences (p?<?0.05) only in the number of ampules required.

Conclusions.?Maternal age adversely affected ovarian performance. During repeated IVF cycles we also noted an age-independent decline of ovarian response.