Looking past the appearance: a comprehensive description of the clinical contribution of poor-quality blastocysts to increase live birth rates during cycles with aneuploidy testing

Study question: Which are the clinical benefits and risks of including poor-quality blastocysts (PQBs) in the cohort of biopsied embryos during a cycle with preimplantation genetic testing for aneuploidies (PGT-A)? Summary answer: PQBs show a worse prognosis with respect to sibling non-PQBs, but their clinical use allows an overall 2.6% increase in the number of live births (LBs) achievable after PGT-A. What is known already: PQBs

Maternal effect factors that contribute to oocytes developmental competence: an update

: Oocyte developmental competence is defined as the capacity of the female gamete to be fertilized and sustain development to the blastocyst stage. Epigenetic reprogramming, a correct cell division pattern, and an efficient DNA damage response are all critical events that, before embryonic genome activation, are governed by maternally inherited factors such as maternal-effect gene (MEG) products. Although these molecules are stored inside the oocyte until ovulation and exert their main role during fertilization and preimplantation development, some of them are already functioning during folliculogenesis and oocyte meiosis resumption. This mini review summarizes the crucial roles played by MEGs during oocyte maturation, fertilization, and preimplantation development with a direct/indirect effect on the acquisition or maintenance of oocyte competence. Our aim is to inspire future research on a topic with potential clinical perspectives for the prediction and treatment of female infertility

Biochemical pregnancy loss after frozen embryo transfer seems independent of embryo developmental stage and chromosomal status

Biochemical pregnancy loss (BPL), defined as serum beta-human chorionic gonadotropin levels ≥50 IU/l in at least two pregnancy tests, not associated with any ultrasonographical evidence of pregnancy, is often attributed to chromosomal abnormalities; however, no hard evidence exists to support this hypothesis. Are any IVF cycle parameters associated with the occurrence of a BPL? Retrospective study aimed at evaluating the effect of embryo developmental stage at transfer and chromosomal assessment on the BPL rate in IVF after frozen embryo transfer (FET). Specifically, 641 FET of 1179 cleavage stage untested embryos (Group A), 1021 FET of 1259 untested blastocyst stage embryos (Group B), and 789 blastocyst stage FET of 803 euploid embryos (Group C) were performed in a 6-year period. Only FET were evaluated to avoid a potential effect of ovarian stimulation on endometrial receptivity. The BPL rates were similar (n = 30/217, 13.8% in Group A; n = 37/412, 9.0% in Group B; n = 42/433, 9.7% in Group C). Neither embryo developmental stage at FET nor chromosomal assessment showed a correlation with BPL. Furthermore, logistic regression analyses did not show any association between BPL and patient, cycle and/or transfer characteristics. BPL seems independent of the embryo's developmental stage, the use of trophectoderm biopsy and the chromosomal constitution at FET. Similar BPL rates after transferring euploid blastocysts compared with both untested cleavage and blastocyst stage embryos suggest investigating the role of endometrial and other embryonic factors putatively involved in the process of implantation

Biomechanical forces and signals operating in the ovary during folliculogenesis and their dysregulation: implications for fertility

Background: Folliculogenesis occurs in the highly dynamic environment of the ovary. Follicle cyclic recruitment, neo-angiogenesis, spatial displacement, follicle atresia and ovulation stand out as major events resulting from the interplay between mechanical forces and molecular signals. Morphological and functional changes to the growing follicle and to the surrounding tissue are required to produce oocytes capable of supporting preimplantation development to the blastocyst stage. Objective and rationale: This review will summarize the ovarian morphological and functional context that contributes to follicle recruitment, growth and ovulation, as well as to the acquisition of oocyte developmental competence. We will describe the changes occurring during folliculogenesis to the ovarian extracellular matrix (ECM) and to the vasculature, their influence on the mechanical properties of the ovarian tissue, and, in turn, their influence on the regulation of signal transduction. Also, we will outline how their dysregulation might be associated with pathologies such as polycystic ovary syndrome (PCOS), endometriosis or premature ovarian insufficiency (POI). Finally, for each of these three pathologies, we will highlight therapeutic strategies attempting to correct the altered biomechanical context in order to restore fertility. Search methods: For each area discussed, a systematic bibliographical search was performed, without temporal limits, using PubMed Central, Web of Science and Scopus search engines employing the keywords extracellular matrix, mechanobiology, biomechanics, vasculature, angiogenesis or signalling pathway in combination with: ovary, oogenesis, oocyte, folliculogenesis, ovarian follicle, theca, granulosa, cumulus, follicular fluid, corpus luteum, meiosis, oocyte developmental competence, preimplantation, polycystic ovary syndrome, premature ovarian insufficiency or endometriosis. Outcomes: Through search engines queries, we yielded a total of 37 368 papers that were further selected based on our focus on mammals and, specifically, on rodents, bovine, equine, ovine, primates and human, and also were trimmed around each specific topic of the review. After the elimination of duplicates, this selection process resulted in 628 papers, of which 287 were cited in the manuscript. Among these, 89.2% were published in the past 22 years, while the remaining 8.0%, 2.4% or 0.3% were published during the 1990s, 1980s or before, respectively. During folliculogenesis, changes occur to the ovarian ECM composition and organization that, together with vasculature modelling around the growing follicle, are aimed to sustain its recruitment and growth, and the maturation of the enclosed oocyte. These events define the scenario in which mechanical forces are key to the regulation of cascades of molecular signals. Alterations to this context determine impaired folliculogenesis and decreased oocyte developmental potential, as observed in pathological conditions which are causes of infertility, such as PCOS, endometriosis or POI. Wider implications: The knowledge of these mechanisms and the rules that govern them lay a sound basis to explain how follicles recruitment and growth are modulated, and stimulate insights to develop, in clinical practice, strategies to improve follicular recruitment and oocyte competence, particularly for pathologies like PCOS, endometriosis and POI

Maternal body mass index associates with blastocyst euploidy and live birth rates: the tip of an iceberg?

Research question: Does maternal preconceptional body mass index (BMI) associate with mean blastocyst euploidy rate (m-ER) per patient and live birth rate (LBR) after vitrified-warmed euploid single embryo transfer (SET)? Design: Observational study conducted between April 2013 and March 2020 at a private IVF clinic, involving 1811 Caucasian women undergoing trophectoderm biopsy and comprehensive chromosome testing. The outcomes of 1125 first vitrified-warmed euploid SET were also analysed. Patients were clustered as normal weight (BMI 18.5-25; n = 1392 performing 859 SET), underweight (BMI <18.5; n = 160 performing 112 SET) and overweight (BMI >25; n = 259 performing 154 SET). m-ER per patient was the primary outcome. The secondary outcomes were all clinical outcomes per euploid SET. All data were adjusted for confounders through regression analyses. Results: The m-ER per patient decreases as maternal BMI increases from 17 up to 22-23 before reaching a plateau. A linear regression adjusted for maternal age confirmed this moderate association (unstandardized coefficient B: -0.6%, 95% confidence interval [CI]: -1.1 to -0.1%, P = 0.02). All clinical outcomes were similar between normal weight and underweight women. Overweight women, instead, showed higher miscarriage rate per clinical pregnancy (n = 20/75, 26.7% versus n = 67/461, 14.5%; odds ratio [OR] adjusted for blastocyst quality and day of full blastulation: 2.0, 95% CI: 1.1-3.6, P = 0.01) and lower LBR per SET (n = 55/154, 35.7% versus n = 388/859, 45.2%; OR adjusted for blastocyst quality and day of full blastulation: 0.67, 95% CI: 0.46-0.96, P = 0.03). Conclusion: These data indicate a need for future research on more sensitive metrics to assess body fat mass and distribution, as well as on the mechanisms leading to lipotoxicity, thereby impairing embryo competence and/or endometrial receptivity. Overweight women should be informed of their higher risk for miscarriage and, whenever possible, encouraged to lose weight, especially before transfer