Distinct mRNA expression profiles and miRNA regulators of the PI3K/AKT/mTOR pathway in breast cancer: insights into tumor progression and therapeutic targets.

Background: Breast cancer remains a leading cause of mortality among women, driven by the molecular complexity of its various subtypes. This study aimed to investigate the differential expression of genes and miRNAs involved in the PI3K/AKT/mTOR signaling pathway, a critical regulator of cancer progression.

Methods: We analyzed tumor tissues from five breast cancer subtypes-luminal A, luminal B HER2-negative, luminal B HER2-positive, HER2-positive, and triple-negative breast cancer (TNBC)-and compared them with non-cancerous tissues.

How do health professionals react to clinical guidelines? Grit to cope with unpredictable situations and limitations not addressed by guidelines.

Assisted Reproductive Medicine (ART) has become the primary treatment of infertility. As such, ART has been regulated by certain authorities and primarily, structured by various scientific organisms through recommendations and guidelines. Yet, these have limits - the topic addressed here - and may at times need to rely on grit for managing the totally unexpected.

Effect of overweight and obesity on live birth rate in single euploid frozen embryo transfers.

Research Question: Does endometrial preparation using a natural cycle lead to higher live birth rates (LBR) in single euploid frozen embryo transfers (FET) compared with programmed cycles, for women who are normal weight, overweight and obese.

Design: Retrospective study of 845 single euploid FETs from 688 couples. Patients were stratified by body mass index (BMI) into normal weight, overweight and obesity class I/II categories.

Association between iron deficiency and fertility.

Introduction: This retrospective, observational cohort study investigated the association between treatment of iron deficiency with conception results and pregnancy outcomes in women with infertility and iron deficiency, before and after intravenous ferric carboxymaltose infusion.

Material And Methods: Data were collected from electronic health records from the Dextra Fertility Clinic (Helsinki, Finland) between 2015 and 2020. The cohort included 292 women (<43 years) with infertility and iron deficiency (s-ferritin ≤30 μg/L), treated with a ferric carboxymaltose infusion (Ferinject®, 500 mg i.

Novel and recurrent genetic variants associated with male and female infertility.

Recently, the knowledge of the genetic basis of fertility disorders has expanded enormously, mainly thanks to the use of next-generation sequencing (NGS). However, the genetic cause of infertility, in the majority of patients, is still undefined. The aim was to identify novel and recurrent pathogenic/likely pathogenic variants in patients with isolated infertility or puberty delay using a targeted NGS technique.

Artificial removal of the zona pellucida at the pronuclear stage: an exploratory study to improve embryo fragmentation.

Objective: To investigate whether artificial removal of zona pellucida (ZP) at the pronuclear stage improves good-quality embryos and blastocyst development in patients with difficulty conceiving because of severe fragmentation in early-cleavage stage.

Design: Exploratory investigation.

Setting: Reproductive center.

Fertility journey of a patient with McCune-Albright syndrome associated with bilateral ovarian involvement.

Objective: To report a patient with McCune-Albright syndrome (MAS) with bilateral ovarian involvement who had achieved a pregnancy through in vitro fertilization (IVF).

Design: Case report.

Setting: Academic fertility center.

Varicocele repair for severe oligoasthenoteratozoospermia: Scoping review of published guidelines, and systematic review of the literature.

Background: The outcomes of varicocele repair (VR) for severe oligozooasthenoteratozoospermia (OAT) have not been widely examined.

Methods: Assessment of outcomes of VR after severe OAT, employing scoping review of published guidelines, and systematic review of literature. The Newcastle-Ottawa scale appraised the quality of included studies.

Oocyte yield and live birth rate after follitropin delta dosing and fresh embryo transfer: an individual patient data meta-analysis.

Research Question: What number of retrieved oocytes is associated with the optimum chance of achieving a live birth for women undergoing ovarian stimulation with individualized follitropin delta?

Design: An individual patient data meta-analysis was performed on 1772 patients from five randomized controlled trials using individualized follitropin delta for ovarian stimulation with fixed daily dosing based on serum anti-Müllerian hormone (AMH) level and body weight. Live birth rate (LBR) and ovarian hyperstimulation syndrome (OHSS) were evaluated in relation to the number of oocytes retrieved. Predicted LBR was obtained using a logistic regression analysis with fractional polynomials.

Ovarian sensitivity index affects clinical pregnancy and live birth rates in gonadotropin-releasing hormone agonist and antagonist fertilization cycles.

Objectives: This study aimed to investigate the correlation of ovarian sensitivity index (OSI) and clinical parameters in IVF treatments.

Methods: IVF data files between January 2011 and December 2020 in a single unit were included. The primary outcome measure was the correlation between the OSI and clinical pregnancy and live birth rates.

FSH/LH co-stimulation in Advanced Maternal Age (AMA) and hypo-responder patients - Arabian gulf delphi consensus group.

Background: In a global effort to assess expert perspectives on the use of recombinant gonadotropins, recombinant human luteinizing hormone (r-hLH) and recombinant human follicle-stimulating hormone (r-hFSH), a consensus meeting was held in Dubai. The key aim was to address three critical questions: What are the factors that influence follicle response to gonadotropins? Which categories of patients are most likely to benefit from LH supplementation? And what are the optimal management strategies for these patients?

Methods: A panel of thirty-six experts reviewed and refined the initial statements and references proposed by the Scientific Coordinator. Consensus was defined as agreement or disagreement by more than two-thirds (66%) of the panel members for each statement.

Impact of cancer during reproductive age on the probability of livebirth after cancer: a register-based cohort study among Danish women aged 18-39 with and without cancer.

Purpose: This register-based study investigates the probability of a livebirth after cancer during the female reproductive age.

Methods: The study population, derived from the DANAC II cohort, included women aged 18-39 diagnosed with cancer between 1978 and 2016, matched with 60 undiagnosed women each from the general population. Primary outcome was a livebirth after cancer with follow-up until death, emigration, or end of follow-up.

Sex differences in childhood cancer risk following ART conception: a registry-based study.

Study Question: Does the risk of childhood cancer following ARTs vary by sex?

Summary Answer: In this registry-based study, some childhood cancers showed positive sex- and age-specific associations in children conceived using certain ART modalities, which were not evident in overall combined analyses.

What Is Known Already: The relationship between ART and risk of childhood cancer has shown diverse outcomes in prior research. Studies examining whether there are sex differences in childhood cancer risk after ART conception are lacking.

Genome-wide DNA methylation and gene expression in human placentas derived from assisted reproductive technology.

Background: Assisted reproductive technology (ART) has been associated with increased risks for growth disturbance, disrupted imprinting as well as cardiovascular and metabolic disorders. However, the molecular mechanisms and whether they are a result of the ART procedures or the underlying subfertility are unknown.

Methods: We performed genome-wide DNA methylation (EPIC Illumina microarrays) and gene expression (mRNA sequencing) analyses for a total of 80 ART and 77 control placentas.

Luteinizing hormone profiles during ovarian stimulation in assisted reproductive treatment.

Introduction: Few data is available on the natural course of luteinizing hormone (LH) during ovarian stimulation, but it has been suggested that 'oversuppressed' LH could decrease fertility outcomes. Our aim with this study is to evaluate the changes in LH depending on the used stimulation protocol to better define LH oversuppressioin.

Methods: Patients undergoing oocyte retrieval in a tertiary fertility center between 01-01-2015 and 30-09-2020 after stimulation with a short-agonist (SA) or antagonist (A) protocol were included.

Transcriptomic analysis and epigenetic regulators in human oocytes at different stages of oocyte meiotic maturation.

Human oocytes are highly specialized cells with the capacity to store and regulate mRNAs during oocyte maturation, in preparation for post-fertilization steps. Here we performed single-oocyte transcriptomic analysis of human oocytes in three meitoic maturation stages - Germinal Vesicle (GV; n = 6), Metaphase I (MI; n = 6) and Metaphase II (MII; n = 7). Single-oocyte transcriptomic analysis revealed that the total number of expressed genes progressively decreased from GV to MII stages, with 9660 genes being transcribed in GV, 8734 in MI and 5889 in MII.

The regulatory interplay between miRNA and DNA methylation orchestrates vital ovarian functions and associated traits in PCOS.

Polycystic ovary syndrome (PCOS) is the leading cause of amenorrhea and anovulatory infertility in women of reproductive age. Both gene polymorphisms and tissue-specific epigenetic alterations, which determine gene transcription and translation dynamics in disease-states, strongly influence PCOS development. Particularly, promoter-proximal DNA methylation and microRNA expression changes show strong associations with follicular defects, suggesting post-transcriptional dysregulation of localized gene networks.

The relationship between controlled ovarian stimulation protocol, meiotic spindle visibility, position of the meiotic spindle relative to the polar body in the human oocyte, and clinical outcomes following ICSI.

Purpose: To investigate the effects of different controlled ovarian stimulation (COS) protocols, including the progestin-primed ovarian stimulation (PPOS), long, short, and the gonadotropin-releasing hormone antagonist protocols, on meiotic spindle visibility and position within the oocyte and clinical outcomes following ICSI.

Methods: Before ICSI, spindle position () just below the polar body (PB) was defined as 0° and categorized as follows:  = 0°, 0° <  ≤ 30°, 30° <  ≤ 60°, 60° <  ≤ 90°, 90° <  ≤ 180°, between the PB and the oolemma, and nonvisible. The clinical outcomes after ICSI were retrospectively analyzed.

Preterm birth in assisted reproduction: the mediating role of hypertensive disorders in pregnancy.

Study Question: To what extent can hypertensive disorders in pregnancy (HDP) explain the higher risk of preterm birth following frozen embryo transfer (frozen-ET) and fresh embryo transfer (fresh-ET) in ART compared with naturally conceived pregnancies?

Summary Answer: HDP did not contribute to the higher risk of preterm birth in pregnancies after fresh-ET but mediated 20.7% of the association between frozen-ET and preterm birth.

What Is Known Already: Risk of preterm birth is higher after ART compared to natural conception.

Psychosocial and physical wellbeing in women and male partners undergoing immediate versus postponed modified natural cycle frozen embryo transfer after ovarian stimulation and oocyte pick-up: a sub-study of a randomized controlled trial.

Study Question: Are there differences in psychosocial and physical wellbeing among women and male partners undergoing modified natural cycle (mNC) frozen embryo transfer (FET) in immediate compared to postponed cycles after ovarian stimulation (OS) and oocyte pick-up (OPU)?

Summary Answer: Significantly more women in the immediate group reported physical symptoms than women in the postponed group whilst fewer were emotionally affected by waiting time, although the latter difference lost statistical significance after adjustment for multiple testing.

What Is Known Already: Infertility and fertility treatment are known to cause psychosocial distress in women and couples longing for a child. The treatment may be long-term and delayed for various reasons, such as the elective postponement of FET after a fresh transfer without pregnancy or an elective freeze-all cycle, possibly further increasing the level of distress.

The First Lugano Workshop on the role of adenomyosis in ART.

Adenomyosis is an important clinical condition with uncertain prevalence, and clinical focus on adenomyosis in patients undergoing assisted reproductive technology (ART) has increased during recent years. Recognizing the limited clinical knowledge on the impact of adenomyosis on ART outcomes, the First Lugano Adenomyosis Workshop was a symposium involving experts in the field of adenomyosis, covering basic research, imaging, surgery and infertility to highlight current advances and future research areas over a wide range of topics related to adenomyosis. Adenomyosis is characterized by altered oestrogen and progesterone signalling pathways.

Do very young oocyte donors negatively impact live birth rates in their recipients?

To understand whether there was an association between very young oocyte donors and adverse outcomes, this was a single centre retrospective study (Lister Fertility Clinic, London) examining data collected between 1st January 2010 and 31st December 2021. A total of 1,182 oocyte donors were included in the final analysis. Data was categorised by donor age in years; ≤22, 23-25, 26-28, 29-31, 32-34.

Real-World Evidence of Dydrogesterone 20 mg and 30 mg SR Usage in Pregnancy.

Background Dydrogesterone, an oral selective progesterone receptor agonist with high bioavailability, has been used since the 1960s to treat various conditions arising due to the deficiency of progesterone. Patients are expected to have additional compliance and reduced pill burden with dydrogesterone 20 mg and 30 mg SR once a day (OD) for conditions requiring 10 mg twice a day (BID) or thrice a day (TID). Methodology A real-world analysis was conducted using the HealthPlix electronic medical records (EMR) database to understand the demography, indications, and prescription patterns of dydrogesterone 20 mg and 30 mg SR, including co-prescriptions.

Ovarian tissue cryopreservation in breast cancer patients: glass half empty or glass half full?

This is a commentary to a paper recently published in RBMOnline by Macklon and De Vos, in which they argue for a discontinuation of ovarian tissue freezing for fertility preservation in women with breast cancer. Instead, they suggest the use of oocyte vitrification following ovarian stimulation as the preferred method of fertility preservation. This commentary presents nine separate arguments that should be considered in the context of ovarian tissue freezing and fertility preservation in girls and women.