Mosaic human preimplantation embryos and their developmental potential in a prospective, non-selection clinical trial.

Chromosome imbalance (aneuploidy) is the major cause of pregnancy loss and congenital disorders in humans. Analyses of small biopsies from human embryos suggest that aneuploidy commonly originates during early divisions, resulting in mosaicism. However, the developmental potential of mosaic embryos remains unclear. We followed the distribution of aneuploid chromosomes across 73 unselected preimplantation embryos and 365 biopsies, sampled from four multifocal trophectoderm (TE) samples and the inner cell mass (ICM). When mosaicism impacted fewer than 50% of cells in one TE biopsy (low-medium mosaicism), only 1% of aneuploidies affected other portions of the embryo. A double-blinded prospective non-selection trial (NCT03673592) showed equivalent live-birth rates and miscarriage rates across 484 euploid, 282 low-grade mosaic, and 131 medium-grade mosaic embryos. No instances of mosaicism or uniparental disomy were detected in the ensuing pregnancies or newborns, and obstetrical and neonatal outcomes were similar between the study groups. Thus, low-medium mosaicism in the trophectoderm mostly arises after TE and ICM differentiation, and such embryos have equivalent developmental potential as fully euploid ones.

Preimplantation Genetic Testing for Aneuploidy Improves Clinical, Gestational, and Neonatal Outcomes in Advanced Maternal Age Patients Without Compromising Cumulative Live-Birth Rate.

PURPOSE: To report the effects of blastocyst stage aneuploidy testing on clinical, gestational, and neonatal outcomes for patients of advanced maternal age undergoing IVF. METHODS: This is a single-center observational-cohort study with 2 years follow-up. The study includes a total of 2538 couples undergoing 2905 egg collections (control group), 308 (PGT-A), and 106 (drop-out group, consenting for PGT-A but withdrawing due to poor embryological outcome) RESULTS: Compared with control group, PGT-A showed improved clinical outcomes (live-birth rate per transferred embryo, LBR 40.3% vs 11.0%) and reduced multiple pregnancy rate (MPR, 0% vs 11.1%) and pregnancy loss (PL, 3.6% vs 22.6%). Drop-out group showed the worst clinical outcomes suggesting that abandoning PGT-A due to poor response to ovarian stimulation is not a favorable option. Cytogenetic analysis of product of conceptions and CVS/amniocentesis showed higher aneuploid pregnancy rates for control group regardless of embryo transfer strategy (0%, 17.9%, and 19.9%, for PGT-A, control day 5 and day 3, respectively). Multivariate analysis showed no negative impact of PGT-A-related interventions on cumulative delivery rate (26.3%, 95% CI 21.5-31.6 vs 24.0%, 95% CI 22.5-25.6 for PGT-A and control, respectively) and on neonatal outcomes. CONCLUSION: PGT-A improves clinical outcomes, particularly by reducing pregnancy loss and chromosomally abnormal pregnancy for patients of advanced maternal age, with no major impact on cumulative live-birth rate (CLBR) per egg retrieval.

Before Is Better: Innovative Multidisciplinary Preconception Care in Different Clinical Contexts.

CONTEXT: Implementation of pre-conception care units is still very limited in Italy. Nowadays, the population's awareness of the reproductive risks that can be reduced or prevented is very low. Purpose and main findings: We presented a new personalized multidisciplinary model of preconception care aimed at identifying and possibly reducing adverse reproductive events. We analyzed three cohorts of population: couples from the general population, infertile or subfertile couples, and couples with a previous history of adverse reproductive events. The proposal involves a deep investigation regarding family history, the personal histories of both partners, and reproductive history. PRINCIPAL CONCLUSIONS: Preconception care is still neglected in Italy and under-evaluated by clinicians involved in natural or in vitro reproduction. Adequate preconception counseling will improve maternal and fetal obstetrical outcomes.

An Observational Retrospective Cohort Trial on 4,828 IVF Cycles Evaluating Different Low Prognosis Patients Following the POSEIDON Criteria.

Objective: To study the actual controlled ovarian stimulation (COS) management in women with suboptimal response, comparing clinical outcomes to the gonadotropins consume, considering potential role of luteinizing hormone (LH) addition to follicle-stimulating hormone (FSH). Design: Monocentric, observational, retrospective, real-world, clinical trial on fresh intra-cytoplasmic sperm injection (ICSI) cycles retrieving from 1 to 9 oocytes, performed at Humanitas Fertility Center from January 1st, 2012 to December 31st, 2015. Methods: COS protocols provided gonadotropin releasing-hormone (GnRH) agonist long, flare-up, short and antagonist. Both recombinant and urinary FSH were used for COS and LH was added according to the clinical practice. ICSI outcomes considered were: gonadotropins dosages; total, mature, injected and frozen oocytes; cumulative, transferred and frozen embryos; implantation rate; pregnancy, delivery and miscarriage rates. Outcomes were compared according to the gonadotropin regimen used during COS. Results: Our cohort showed 20.8% of low responders, defined as 1-3 oocytes retrieved and 79.2% of "suboptimal" responders, defined as 4-9 oocytes retrieved. According to recent POSEIDON stratification, cycles were divided in group 1 (6.9%), 2 (19.8%), 3 (11.7%), and 4 (61.5%). The cohort was divided in 3 groups, according to the gonadotropin's regimen. Women treated with FSH plus LH showed worst prognostic factors, in terms of age, basal FSH, AMH, and AFC. This difference was evident in suboptimal responders, whereas only AMH and AFC were different among treatment groups in low responders. Although a different result, in terms of oocytes and embryos detected, major ICSI outcomes (i.e., pregnancy and delivery rates) were similar among groups of COS treatment. Outcomes were significantly different among Poseidon groups. Implantation, pregnancy and delivery rates were significantly higher in Poseidon group 1 and progressively declined in other POSEIDON groups, reaching the worst percentage in group 4. Conclusions: In clinical practice, women with worst prognosis factors are generally treated with a combination of LH and FSH. Despite low prognosis women showed a reduced number of oocytes retrieved, the final ICSI outcome, in terms of pregnancy, is similarly among treatment group. This result suggests that the LH addition to FSH during COS could improve the quality of oocytes retrieved, balancing those differences that are evident at baseline. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03290911.

The prevalence of retinal angiomatous proliferation in age-related macular degeneration with occult choroidal neovascularization.

BACKGROUND: The purpose of the study was to ascertain the prevalence of retinal angiomatous proliferation (RAP) by means of dynamic indocyanine green angiography (d-ICGA) in patients with newly diagnosed fibrovascular pigment epithelium detachment (type 1) or late leakage of undetermined source (type 2) occult choroidal neovascularization (CNV) on fluorescein angiography. METHODS: We carried out a review of digital fluorescein and ICG angiograms obtained by confocal scanning laser ophthalmoscope (HRA; Heidelberg Engineering GmbH, Dossenheim, Germany) in 253 consecutive patients (270 eyes) with a clinical diagnosis of type 1 or type 2 occult CNV on fluorescein angiography (1998 through 2003). RESULTS: Sixty eyes had type 1 and 210 eyes type 2 occult CNV on fluorescein angiography. Overall, 57 cases of RAP were identified in 54 eyes (20%) with d-ICGA. RAP was present in 6 out of 60 eyes with type 1 (10%) and in 51 out of 210 eyes with type 2 occult CNV (24%). Mean distance of the lesion from the fovea was 682 +/- 304 microm (mean +/- SD). CONCLUSIONS: d-ICGA is invaluable for early diagnosis of RAP in exudative age-related macular degeneration (ARMD). In our series, up to one fourth of type 2 occult CNV were in fact RAP.

Rural surgery in southern Sudan.

INTRODUCTION: This article reports a retrospective analysis of a 6-year experience of providing surgical care in remote areas of southern Sudan under extremely adverse conditions. METHODS: Teams of expatriate consultants (surgeon, anesthetist, scrub nurse) carried out 28 "surgical missions" with the aims of treating surgical cases previously selected and of training local personnel in basic surgery on the job. RESULTS: A total of 1642 patients (71% males, 30% under the age of 16) have undergone an operation. Altogether, 1264 elective procedures (77%) and 378 emergency procedures (23%) were performed. Hernia surgery comprised the main workload, followed by proctologic and gynecologic operations. Most operations were performed under spinal anesthesia. Other cases required ketamine, and a small number of patients had local anesthesia. There were 14 fatal complications, most of them related to the delay in obtaining medical attention. Based on the training results, the Sudanese personnel of two of the five health centers involved in the program are already fully autonomous. Two doctors and two nurses are proficient in essential surgery; two not qualified nurses are proficient in "primary" anesthesia; and others are proficient in scrubbing and surgical nursing. CONCLUSIONS: This report demonstrates that it is feasible to establish surgical services in rural areas of developing countries by utilizing simple facilities, providing them with basic equipment, and employing local personnel selected and trained on the job by teams composed of a consultant surgeon, anesthetist, and scrub nurse. This seems to be the only realistic possibility for providing surgical care to the rural populations of the least developed countries.