Recombinant human luteinizing hormone co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age: a systematic review and meta-analysis of randomized controlled trials.

Introduction: Several studies suggest that luteinizing hormone (LH) could improve IVF outcome in women of advanced reproductive age by optimizing androgen production. In this review, we assessed the role of recombinant-human LH (r-hLH) and recombinant human follicle stimulating hormone (r-hFSH) co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age candidates for assisted reproduction.

Material And Methods: Using a preregistered protocol we systematically searched Medline/PubMed, Scopus and the ISI Web of Science databases to identify randomized controlled trials in which r-hFSH monotherapy protocols were compared with r-hFSH/r-hLH co-treatment in women ≥35 years undergoing fresh IVF cycles.

Phthalates and Bisphenol A: Presence in Blood Serum and Follicular Fluid of Italian Women Undergoing Assisted Reproduction Techniques.

Background: folliculogenesis is a strictly regulated process that may be affected by endocrine disrupting chemicals (EDCs) through sometimes not so clear molecular mechanisms.

Methods: we conducted a multicentric observational study involving six fertility centers across Italy, prospectively recruiting 122 women attending a fertility treatment. Recruited women had age ≤42 years, and normal ovarian reserve.

DuoStim - a reproducible strategy to obtain more oocytes and competent embryos in a short time-frame aimed at fertility preservation and IVF purposes. A systematic review.

Recent evidence suggests that follicular development occurs in a wave-like model during the ovarian cycle, where up to three cohorts of follicles are recruited to complete folliculogenesis. This understanding overtakes the previous dogma stating that follicles grow only during the follicular phase of the menstrual cycle. Therefore, in fertilization (IVF), novel protocols regarding ovarian stimulation have been theorized based on the use of gonadotrophins to prompt the growth of antral follicles at any stage of the menstrual cycle.

The effect of ICSI-related procedural timings and operators on the outcome.

Study Question: Do the ICSI-related procedural timings and operators affect the outcomes of an ART cycle?

Summary Answer: The ICSI-related timings and operators do not associate with the mean blastulation rate per cohort of inseminated oocytes and the cumulative delivery rate per concluded cycle, except for a mild association between the times from induction of ovulation to oocyte denudation and the former outcome.

What Is Known Already: In ART, specific timings, protocols and conditions must be complied with to preserve gamete developmental and reproductive competence during the required manipulations. ICSI represents a groundbreaking advancement that has been widely implemented.

Time of morulation and trophectoderm quality are predictors of a live birth after euploid blastocyst transfer: a multicenter study.

Objective: To investigate whether the morphodynamic characterization of a euploid blastocyst's development allows a higher prediction of a live birth after single-embryo-transfer (SET).

Design: Observational cohort study conducted in two phases: training and validation.

Setting: Private in vitro fertilization centers.

Luteal phase after conventional stimulation in the same ovarian cycle might improve the management of poor responder patients fulfilling the Bologna criteria: a case series.

Objective: To assess the clinical contribution of luteal-phase stimulation (LPS) to follicular-phase stimulation (FPS) in a single ovarian cycle (DuoStim) for poor responder patients fulfilling the Bologna criteria.

Design: Observational study (years 2015-2017) including women satisfying ≥2 of the following characteristics: maternal age ≥40 years and/or ≤3 oocytes retrieved after previous conventional stimulation and/or reduced ovarian reserve (i.e.

Human Blastocyst Biopsy and Vitrification.

Blastocyst biopsy is performed to obtain a reliable genetic diagnosis during IVF cycles with preimplantation genetic testing. Then, the ideal workflow entails a safe and efficient vitrification protocol, due to the turnaround time of the diagnostic techniques and to transfer the selected embryo(s) on a physiological endometrium in a following natural cycle. A biopsy approach encompassing the sequential opening of the zona pellucida and retrieval of 5-10 trophectoderm cells (ideally 7-8) limits both the number of manipulations required and the exposure of the embryo to sub-optimal environmental conditions.

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 ( View Article and Find Full Text PDF

The main will of the patients of a private Italian IVF clinic for their aneuploid/affected blastocysts would be donation to research: a currently forbidden choice.

Purpose: Surplus cryopreserved affected/aneuploid blastocysts may be obtained after in vitro fertilization (IVF) treatments with preimplantation genetic testing (PGT). These embryos are considered not suitable for transfer and may be discarded. Currently, in Italy, an embryo disposition decision (EDD) is not allowed and the frozen/vitrified blastocysts (even if affected/aneuploid) should be kept cryopreserved indefinitely.

State of the art and emerging drug therapies for female infertility.

At present, infertility is a key-issue. When applicable, fertilization (IVF) has become the standard approach to treat this condition but a thorough investigation and, whenever possible, the individual diagnosis of the underlying causes of infertility are required. For many female causes, indeed, efficient medical therapies are available to achieve a fast solution of the problem.

Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment.

Advanced maternal age (AMA; >35 year) is associated with a decline in both ovarian reserve and oocyte competence. At present, no remedies are available to counteract the aging-related fertility decay, however different therapeutic approaches can be offered to women older than 35 year undergoing IVF. This review summarizes the main current strategies proposed for the treatment of AMA: (i) oocyte cryopreservation to conduct fertility preservation for medical reasons or "social freezing" for non-medical reasons, (ii) personalized controlled ovarian stimulation to maximize the exploitation of the ovarian reserve in each patient, (iii) enhancement of embryo selection via blastocyst-stage preimplantation genetic testing for aneuploidies and frozen single embryo transfer, or (iv) oocyte donation in case of minimal/null residual chance of pregnancy.

An integrated investigation of oocyte developmental competence: expression of key genes in human cumulus cells, morphokinetics of early divisions, blastulation, and euploidy.

Purpose: To investigate the association of cumulus cell (CC)-related expression of a selected cluster of key genes (PTGS2, CAMK1D, HAS2, STC1, and EFNB2) with embryo development to blastocyst.

Methods: Exploratory study at a private clinic. Eighteen advanced maternal age patients were enrolled (37.

Associations of blastocyst features, trophectoderm biopsy and other laboratory practice with post-warming behavior and implantation.

Study Question: Are trophectoderm biopsy or other pre-vitrification features or laboratory practices associated with differences in blastocyst post-warming behavior (degeneration, re-expansion and live birth after single embryo transfer (SET))?

Summary Answer: Blastocyst morphology, day of full development and artificial shrinkage (either laser-assisted or biopsy-induced) are the pre-vitrification parameters/practices most strongly associated with post-warming behavior and implantation potential while there was no association with trophectoderm biopsy.

What Is Known Already: Since the introduction of vitrification, the adoption of cycle segmentation, freeze-all and SET policies, as well of trophectoderm biopsy-based aneuploidy testing (i.e.

Inconclusive chromosomal assessment after blastocyst biopsy: prevalence, causative factors and outcomes after re-biopsy and re-vitrification. A multicenter experience.

Study Question: Can a second round of biopsy, vitrification and chromosomal testing provide a valid diagnosis where the first attempt fails?

Summary Answer: The risk of inconclusive chromosomal-assessment after trophectoderm biopsy was 2.5% but a further biopsy and vitrification-warming appeared not to impair the competence of euploid blastocysts.

What Is Known Already: The increasing implementation of multicell trophectoderm biopsy has significantly reduced the risk of inconclusive diagnosis after preimplantation-genetic-testing (PGT).

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.

Double Stimulation in the Same Ovarian Cycle (DuoStim) to Maximize the Number of Oocytes Retrieved From Poor Prognosis Patients: A Multicenter Experience and SWOT Analysis.

A panel of experts known as the POSEIDON group has recently redefined the spectrum of poor responder patients and introduced the concept of suboptimal response. Since an ideal management for these patients is still missing, they highlighted the importance of tailoring the ovarian stimulation based on the chance of each woman to obtain an euploid blastocyst. Interestingly, a novel pattern of follicle recruitment has been defined: multiple waves may arise during a single ovarian cycle.

Luteal phase anovulatory follicles result in the production of competent oocytes: intra-patient paired case-control study comparing follicular versus luteal phase stimulations in the same ovarian cycle.

Study Question: Are the mean numbers of blastocysts obtained from sibling cohorts of oocytes recruited after follicular phase and luteal phase stimulations (FPS and LPS) in the same ovarian cycle similar?

Summary Answer: The cohorts of oocytes obtained after LPS are larger than their paired-FPS-derived cohorts and show a comparable competence, thus resulting in a larger mean number of blastocysts.

What Is Known Already: Three theories of follicle recruitment have been postulated to date: (i) the 'continuous recruitment' theory, (ii) the 'single recruitment episode' theory and (iii) the 'wave' theory. Yet, a clear characterization of this crucial biological process for human reproduction is missing.

Prevalence of XXY karyotypes in human blastocysts: multicentre data from 7549 trophectoderm biopsies obtained during preimplantation genetic testing cycles in IVF.

Study Question: Which is the prevalence of a 47,XXY karyotype in human blastocysts biopsied during preimplantation genetic testing for aneuploidies (PGT-A) cycles?

Summary Answer: The prevalence of a 47,XXY karyotype amongst male blastocysts without autosomal aneuploides is ~1%.

What Is Known Already: The prevalence of Klinefelter syndrome is estimated as 0.1-0.

What is new in the management of poor ovarian response in IVF?

Purpose Of Review: The management and treatment of patients with poor ovarian response is still a controversial issue in IVF. Increasing evidences demonstrate that the number of oocytes retrieved after a controlled ovarian stimulation (COS) greatly influences the clinical outcome in terms of cumulative live birth per started cycle. For this reason, any COS should aim to optimize the number of oocytes according to the ovarian reserve of the patient.

Pre-implantation genetic testing in ART: who will benefit and what is the evidence?

Pre-implantation genetic diagnosis for aneuploidy testing (PGD-A) is a tool to identify euploid embryos during IVF. The suggested populations of patients that can benefit from it are infertile women of advanced maternal age, with a history of recurrent miscarriages and/or IVF failures. However, a general consensus has not yet been reached.