Differences in pregnancy outcomes in donor egg frozen embryo transfer (FET) cycles following preimplantation genetic screening (PGS): a single center retrospective study

PURPOSE: This study aims to test the hypothesis, in a single-center retrospective analysis, that live birth rates are significantly different when utilizing preimplantation genetic screening (PGS) compared to not utilizing PGS in frozen–thawed embryo transfers in our patients that use eggs from young, anonymous donors. The question therefore arises of whether PGS is an appropriate intervention for donor egg cycles. METHODS: Live birth rates per cycle and live birth rates per embryo transferred after 398 frozen embryo transfer (FET) cycles were examined from patients who elected to have PGS compared to those who did not. Blastocysts derived from donor eggs underwent trophectoderm biopsy and were tested for aneuploidy using array comparative genomic hybridization (aCGH) or next-generation sequencing (NGS), then vitrified for future use (test) or were vitrified untested (control). Embryos were subsequently warmed and transferred into a recipient or gestational carrier uterus. Data was analyzed separately for single embryo transfer (SET), double embryo transfer (DET), and for own recipient uterus and gestational carrier (GC) uterus recipients. RESULTS: Rates of implantation of embryos leading to a live birth were significantly higher in the PGS groups transferring two embryos (DET) compared to the no PGS group (GC, 72 vs. 56 %; own uterus, 60 vs. 36 %). The live birth implantation rate in the own uterus group for SET was higher in the PGS group compared to the control (58 vs. 36 %), and this almost reached significance but the live birth implantation rate for the SET GC group remained the same for both tested and untested embryos. Live births per cycle were nominally higher in the PGS GC DET and own uterus SET and DET groups compared to the non-PGS embryo transfers. These differences almost reached significance. The live birth rate per cycle in the SET GC group was almost identical. CONCLUSIONS: Significant differences were noted only for DET; however, benefits need to be balanced against risks associated with multiple pregnancies. Results observed for SET need to be confirmed on larger series and with randomized cohorts

Natural cycle results in lower implantation failure than ovarian stimulation in advanced-age poor responders undergoing IVF. fertility outcomes from 585 patients

To compare pregnancy rate and implantation rate in poor responder women, aged over 40 years, who underwent natural cycle versus conventional ovarian stimulation. This is a retrospective single-center cohort study conducted at the GENERA IVF program, Rome, Italy, between September 2012 and December 2018, including only poor responder patients, according to Bologna criteria, of advanced age, who underwent IVF treatment through Natural Cycle or conventional ovarian stimulation. Between September 2012 and December 2018, 585 patients were included within the study. Two hundred thirty patients underwent natural cycle and 355 underwent conventional ovarian stimulation. In natural cycle group, both pregnancy rate per cycle (6.25 vs 12.89%, respectively, p = 0.0001) and pregnancy rate per patient101 with at least one embryo-transfer (18.85 vs 28.11% respectively, p = 0.025) resulted significant reduced. Pregnancy rate per patient managed with conventional ovarian stimulation resulted not significantly different compared with natural cycle (19.72 vs 15.65% respectively, p = 0.228), but embryo implantation rate was significantly higher in patients who underwent natural cycle rather than patient subjected to conventional ovarian stimulation (13 vs 8.28% respectively, p = 0.0468). No significant difference could be detected among the two groups in terms of abortion rate (p = 0.2915) or live birth pregnancy (p = 0.2281). Natural cycle seems to be a valid treatment in patients over 40 years and with a low ovarian reserve, as an alternative to conventional ovarian stimulation

Open versus closed systems for vitrification of human oocytes and embryos

Vitrification is now the dominant approach for cryopreservation of human oocytes and embryos; however, serious disagreement persists, particularly about biosafety issues. Techniques are categorized as either 'open' or 'closed' according to occurrence of direct contact between the medium and liquid nitrogen during cryopreservation. Advocates of closed systems emphasize the potential danger of disease transmission mediated through liquid nitrogen, and praise the safety of their approach; those who use the open systems refer to the lack of evidence of disease transmission and regard their systems as more consistent and efficient. The purpose of this review is to clarify whether open and closed systems are really open and closed; if closed systems are safe and free of any danger of contamination; if closed systems are equally efficient as open ones for cryopreservation of human embryos and oocytes by considering overall outcome; and finally, if ethical and legal concerns are sound when risks and benefits are considered in a broader sense. On the basis of these answers, implementation of rational measures to lower the theoretical danger of disease transmission are proposed while maintaining the achievements in cryopreservation that have contributed substantially to the advancement in assisted reproduction techniques during the past decade

Impact of Maternal Age on Oocyte and Embryo Competence

The overall success of human reproduction, either spontaneously or after IVF, is highly dependent upon maternal age. The main reasons for age-related infertility include reduced ovarian reserve and decreased oocyte/embryo competence due to aging insults, especially concerning an increased incidence of aneuploidies and possibly decreased mitochondrial activity. Age-related chromosomal abnormalities mainly arise because of meiotic impairments during oogenesis, following flawed chromosome segregation patterns such as non-disjunction, premature separation of sister chromatids, or the recent reverse segregation. In this review, we briefly discuss the main mechanisms putatively impaired by aging in the oocytes and the deriving embryos. We also report the main strategies proposed to improve the management of advanced maternal age women in IVF: fertility preservation through oocyte cryopreservation to prevent aging; optimization of the ovarian stimulation and enhancement of embryo selection to limit its effects; and oocyte donation to circumvent its consequences

The Impact of Unbalanced Maternal Nutritional Intakes on Oocyte Mitochondrial Activity: Implications for Reproductive Function.

Abstract Accumulating evidence on the effect of nutrition on reproduction is emerging from both animal and human studies. A healthy dietary pattern and nutrient supplementation, especially during the peri-conceptional period, might be helpful to achieve a live birth, although the mechanisms implicated are not fully understood. The endocrine system and the ooplasmic organelles apparatus, in particular the mitochondria, are clearly key elements during oogenesis and subsequent embryo development, and their proper functioning is associated with nutrition, even beyond maternal aging. Several studies in animal models have reported various adverse effects on mitochondria caused by unbalanced dietary intakes such as high fat diet, high fat high sugar diet, and low protein diet. The alterations produced might include mitochondrial intracellular distribution, content, structure, biogenesis, and functioning. This review summarizes the key role of mitochondria in female reproduction and the effects of different dietary macronutrient compositions on oocyte mitochondrial activity with their possible short-, medium-, and long-term effects

Perspectives in Gamete and Embryo Cryopreservation

Cryopreserved gametes and embryos are a major feature of human-assisted reproduction and patient care services, accounting for an increasing number of births worldwide. Since the first success obtained using frozen human spermatozoa, cryopreservation technology has been successfully extended to include oocytes and embryos, in a variety of both medical and nonmedical indications. Over the years, the available procedures have become widely implemented and the increasing evidence of its efficacy has contributed to acceptance of the technology. Nevertheless, a gold standard protocol that would be universally shared by clinics has yet to be definitively established and, therefore, research into cryopreservation of gametes and embryos cannot be considered concluded. Moreover, much effort should be committed to the definition and resolution of safety issues, the establishment of automation, and investigations about the potentiality of immature germ cells or stem cells

Which key performance indicators are most effective in evaluating and managing an in vitro fertilization laboratory?

The laboratory is the heart of an in vitro fertilization (IVF) clinic, and a quality management system is critical for its administration. We review the main structural, process, and outcome key performance indicators (KPIs) to provide laboratory managers with concrete tools aimed at enhancing the quality of their work. Three concepts must be stressed when dealing with KPIs in IVF: [1] always consider the three types of indicators (structural, process, and outcome related), [2] carefully adapt the control chart to either promptly identify issues and adopt corrective measures, or redefine the control limits in a process called "progress building," [3] consider that achieving a healthy live birth is a multidisciplinary effort that is subject to several confounders, which must be recognized and accounted for in the analyses. In this regard, future KPIs shared among clinicians and embryologists are desirable to enhance the quality of infertility care for IVF patients

Artificial oocyte activation with calcium ionophore does not cause a widespread increase in chromosome segregation errors in the second meiotic division of the oocyte

Objective: To study the effect of artificial oocyte activation (AOA) on chromosome segregation errors in the meiotic divisions. Design: Prospective cohort study with historical control. Setting: Private/academic IVF centers. Patient(s): Fifty-six metaphase II oocytes were donated from 12 patients who had undergone IVF between June 2008 and May 2009. Intervention(s): Oocytes were activated by 40 minutes' exposure to 100 μM calcium-ionophore. The activated oocyte was tubed and analyzed by array comparative genomic hybridization and/or single-nucleotide polymorphism genotyping and maternal haplotyping (meiomapping). A control sample of embryos derived from normally fertilized oocytes was included for comparison. Main outcome measure(s): Incidence of chromosome segregation errors in artificially activated and normally fertilized oocytes in relation to pronuclear evaluation. Result(s): Of 49 oocytes that survived the warming procedure, thirty-nine (79.6%) activated. Most activated normally, resulting in extrusion of the second polar body and formation of a single or no pronucleus (2PB1PN: 30 of 39, 76.9%; or 2PB0PN: 5 of 39, 12.8%). Twenty-seven of these were analyzed, and 16 (59.3%) were euploid, showing no effect of AOA on meiotic segregation. Single-nucleotide polymorphism analysis of normally activated oocytes confirmed normal segregation of maternal chromosomes. No difference in the proportion of meiosis II type errors was observed between artificially activated oocytes (28.6%; 95% confidence interval 3.7%-71.0%) compared with embryos obtained from normally fertilized oocytes (44.4%; 95% confidence interval 13.7%-78.8%). The abnormally activated oocytes, with ≥2PN (4 of 39, 10.3%) were diploid, indicating a failure to coordinate telophase of meiosis II with polar body extrusion. Conclusion(s): From this preliminary dataset, there is no evidence that AOA causes a widespread increase in chromosome segregation errors in meiosis II. However, we recommend that it be applied selectively to patients with specific indications