Corticosteroids, androgens, progestogens and oestrogens in the endometrial microenvironment, and their association with endometrial progression and function.

Research Question: How does the intracrine action of progestagens, oestrogens, androgens and corticosteroids affect endometrial tissue progression and function?

Design: In this prospective observational study, 76 patients (<50 years old, no uterine pathologies and at least one failed IVF cycle) undergoing endometrial biopsy collection for endometrial evaluation between 2018 and 2021 were included. The concentrations of 11 steroid metabolites (cortisone, cortisol, progesterone, oestrone, 2-methoxyestrone, oestradiol, oestriol, testosterone, androstenedione, 17α-hydroxyprogesterone and 17-hydroxypregnenolone) were measured by ultra-performance liquid chromatography-tandem mass spectrometry in the endometrial tissue samples collected during the mid-secretory phase. Endometrial dating and reproductive outcomes (relative to the next good-quality fresh or frozen embryo transfer after the biopsy) were analysed in relation to endometrial steroid concentrations using Barnard's test; correlations between metabolite concentrations were measured by Pearson's correlation co-efficient.

Higher serum progesterone level has no negative impact on live birth rate in frozen embryo transfer.

Optimal synchronisation between the endometrium and the embryo is key to the success of frozen embryo transfers (FET). It is achieved by administering different doses of exogenous oestrogen and progesterone (P4). The negative impact of low levels of P4 on FET has been reported, but there is a lack of knowledge about which levels are most appropriate.

Predicting risk of endometrial failure: a biomarker signature that identifies a novel disruption independent of endometrial timing in patients undergoing hormonal replacement cycles.

Objective: To propose a new gene expression signature that identifies endometrial disruptions independent of endometrial luteal phase timing and predicts if patients are at risk of endometrial failure.

Design: Multicentric, prospective study.

Setting: Reproductive medicine research department in a public hospital affiliated with private fertility clinics and a reproductive genetics laboratory.

The effectiveness of cervical cerclage in twin pregnancies with a mid-trimester short cervix: A retrospective cohort study.

Objective: To analyze the effectiveness of cerclage in twin pregnancies with a short cervix.

Study Design: Retrospective cohort study performed in two University Institutions in Valencia (Spain) with two different protocols for the management of asymptomatic dichorionic diamniotic twin pregnancies with mid-trimester cervical length ≤ 25 mm: treatment with indomethacin, antibiotics and cerclage (cerclage group) (N = 43) versus expectant management (control group) (N = 37).

Results: The initial cervical length was similar in both groups but detection of a short cervix was performed earlier in the cerclage group (21.

Systemic changes induced by autologous stem cell ovarian transplant in plasma proteome of women with impaired ovarian reserves.

Patients with poor ovarian response (POR) and premature ovarian insufficiency (POI) are challenging to treat, with oocyte donation remaining as the only feasible option to achieve pregnancy in some cases. The Autologous stem cell ovarian transplantation (ASCOT) technique allows follicle development, enabling pregnancies and births of healthy babies in these patients. Previous results suggest that growth factors and cytokines secreted by stem cells are partially responsible for their regenerative properties.

Deciphering reproductive aging in women using a NOD/SCID mouse model for distinct physiological ovarian phenotypes.

Female fertility is negatively correlated with age, with noticeable declines in oocyte quantity and quality until menopause. To understand this physiological process and evaluate human approaches for treating age-related infertility, preclinical studies in appropriate animal models are needed. Thus, we aimed to characterize an immunodeficient physiological aging mouse model displaying ovarian characteristics of different stages during women's reproductive life.

Deciphering a shared transcriptomic regulation and the relative contribution of each regulator type through endometrial gene expression signatures.

Backgorund: While various endometrial biomarkers have been characterized at the transcriptomic and functional level, there is generally a poor overlap among studies, making it unclear to what extent their upstream regulators (e.g., ovarian hormones, transcription factors (TFs) and microRNAs (miRNAs)) realistically contribute to menstrual cycle progression and function.

Bioaccumulation of Non-Essential Trace Elements Detected in Women's Follicular Fluid, Urine, and Plasma Is Associated with Poor Reproductive Outcomes following Single Euploid Embryo Transfer: A Pilot Study.

This study aims to determine the association of non-essential trace elements present in follicular fluid, plasma, and urine with reproductive outcomes of women undergoing intracytoplasmic sperm injection (ICSI), preimplantation genetic testing for aneuploidies (PGT-A) and single frozen euploid embryo transfer (SET/FET). This single-center, prospective cohort study included sixty women undergoing ICSI with PGT-A and SET/FET between 2018 and 2019. Urine, plasma and follicular fluid samples were collected on the vaginal oocyte retrieval day to simultaneously quantify ten non-essential trace elements (i.

The Impact of Essential Trace Elements on Ovarian Response and Reproductive Outcomes following Single Euploid Embryo Transfer.

Essential trace elements are required in extremely small amounts and obtained through diet. This research focuses on detecting major trace elements in different biofluids of sixty women undergoing ICSI with PGT-A and SET/FET at IVI-RMA, New Jersey, and assessing their impact on their IVF outcomes. Urine, plasma, and follicular fluid samples were collected on the vaginal oocyte retrieval day to measure the concentrations of eight essential trace elements (copper, zinc, molybdenum, lithium, selenium, manganese, chromium, and iron) using ICP-MS.

Phytoestrogens Present in Follicular Fluid and Urine Are Positively Associated with IVF Outcomes following Single Euploid Embryo Transfer.

The impact and safety of phytoestrogens, plant-derived isoflavones with estrogenic activity predominantly present in soy, on female reproductive health and IVF outcomes continues to be hotly debated. In this prospective cohort study, 60 women attending IVI-RMA New Jersey undergoing IVF with single frozen embryo transfer (SET/FET) of good-quality euploid blastocyst after PGT-A analysis were recruited. Concentrations of two phytoestrogens (daidzein and genistein) in follicular fluid (FF) and urine (U) were measured by UPLC-MSMS, both collected on vaginal oocyte retrieval day.

Reproductive outcomes of oocyte donation in patients with uterine Müllerian anomalies.

Objective: To evaluate live-birth rates per embryo transfer in patients with uterine Müllerian anomalies (UMAs). Secondary objectives were to compare reproductive outcomes between the normal uterus group, the different UMA types, and UMA subgroups with and without required surgery.

Design: This retrospective study compared two cohorts, one with UMAs and other with normal uteri of our oocyte donation program at 12 Instituto Valenciano De Infertilidad/Reproductive Medicine Associates University affiliated clinics from January 2000 to 2020.

Increased cytotoxic natural killer cells in the endometrium alone cannot be considered the immunological cause of recurrent miscarriage.

Objective: To study the distribution and gene expression of endometrial immune cell populations, especially natural killer (NK) subsets, between assisted reproductive technology patients and healthy donors and explore a possible relationship of these results with patients' killer cell immunoglobulin-like receptor (KIR) genotypes and KIR-human antigen leukocyte-C (HLA-C) binding.

Design: Prospective observational cohort study.

Setting: Clinic and university laboratories.

Ovarian rescue in women with premature ovarian insufficiency: facts and fiction.

The ovary has a comparatively short functional lifespan compared with other organs, and genetic and pathological injuries can further shorten its functional life. Thus, preserving ovarian function should be considered in the context of women with threats to ovarian reserve, such as ageing, premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR). Indeed, one-third of women with POI retain resting follicles that can be reactivated to produce competent oocytes, as proved by the in-vitro activation of dormant follicles.

Single intraovarian dose of stem cell- and platelet-secreted factors mitigates age-related ovarian infertility in a murine model.

Background: Systemic administration of soluble factors from bone marrow-derived stem cells combined with activated platelet-rich plasma (SC-PRP) restored ovarian function, mediated through paracrine signaling, in murine models of chemotherapy-induced ovarian damage and human tissue from poor responder patients. However, the effects against age-related infertility and the efficacy of local administration have not been evaluated yet.

Objective: This study aimed to assess whether a single intraovarian dose of stem cells combined with activated platelet-rich plasma can recover ovarian function, oocyte quality, and developmental competence in older mice.

Pituitary suppression with GnRH agonists before ART may be insufficient to treat women with severe adenomyosis.

Research Question: Does aromatase inhibitor improve IVF outcomes by reducing local oestrogen production in patients with adenomyosis undergoing long-term gonadotrophin-releasing hormone agonist (GnRHa) treatment?

Design: Four patients with severe adenomyosis who failed to improve after long-term treatment (≥3 months) with depot GnRHa received treatment with an aromatase inhibitor for 21 days. Blood oestradiol concentrations were monitored after GnRHa treatment both before and after treatment with an aromatase inhibitor. Women received a transfer of IVF autologous or donor oocytes.

Endometrial gene expression differences in women with coronavirus disease 2019.

Objective: To study the potential effect of coronavirus disease (COVID-19) on the endometrial transcriptome of affected, symptomatic women for the detection of altered gene expression.

Design: Pilot study of the endometrial transcriptomes of women manifesting COVID-19 compared with those of women without COVID-19 undergoing hysteroscopic procedures for benign gynecologic disorders using RNA sequencing.

Setting: Hospital and university laboratories.

Adjustment of progesterone administration after endometrial transcriptomic analysis does not improve reproductive outcomes in women with adenomyosis.

Research Question: Do patients with adenomyosis present a dysregulated endometrial receptivity that can be reversed with personalized embryo transfer (PET) by transcriptomic-based progesterone adjustment, improving IVF outcomes?

Design: A multicentre, retrospective, cohort study that transcriptomically analysed the endometrial receptivity of the endometrium in patients with adenomyosis (n = 81) and healthy women (n = 231). Subsequently, implantation, biochemical and clinical miscarriage, and live birth rates between adenomyosis patients with one previous implantation failure using donor oocytes who received (n = 59) or did not receive (n = 66) PET based on endometrial receptivity, were observed to evaluate if adjusted progesterone improves reproductive outcomes of adenomyosis patients.

Results: Patients with adenomyosis significantly presented an altered endometrial receptivity (non-receptive) compared with healthy patients (53.

Hysterosalpingography is obsolete: hysterosalpingo-contrast foam sonography should be the alternative.

Current evidence suggests that the hysterosalpingo-foam sonography test (HyFoSy) has emerged as a new option to make Fallopian tube assessment easier. Several published studies have compared the different types of tubal patency test available with the accepted gold standard, laparoscopy and dye, endorsing the advantages of HyFoSy over the other techniques. However, the authors wonder why professionals nowadays do not indicate HyFoSy as a first-choice diagnostic tool, with X-ray hysterosalpingography as still the most recommended procedure in outpatients.

The Use of Vaginal Lubricants and Ultrasound Gels Can have Deleterious Effects on Sperm Function.

Context: Some vaginal lubricants and ultrasound gels are known to be detrimental to sperm function and therefore could negatively affect fertility.

Aims: The aim of the current study was to develop a sperm motility index (SMI) to test the sperm toxicity of ultrasound gels and vaginal lubricants used in reproductive medicine.

Settings And Design: Two ultrasound gels (Aquasonic and Kefus) and five vaginal lubricants (Vaginesil™, Velastisa, K-Y Jelly, Control, and Durex) were studied.

Pathways and factors regulated by bone marrow-derived stem cells in human ovarian tissue.

Objective: To describe molecular and paracrine signaling changes produced by human bone marrow-derived stem cells (BMDSC) in human ovarian cortex.

Design: Experimental study.

Setting: University hospital research laboratories.

Novel therapeutic targets to improve IVF outcomes in endometriosis patients: a review and future prospects.

Background: Patients with endometriosis often experience infertility and have poor IVF outcomes, with low fertilization and pregnancy rates. Although many theories have tried to explain the mechanisms underlying infertility in these patients, none of them is conclusive.

Objective And Rationale: In this review, we discuss the pathologic mechanisms through which endometriosis likely leads to infertility along with the therapeutic options used to date to treat endometriosis-related infertility and, thereby, to improve IVF outcomes in patients with endometriosis.

Use of dopamine agonists to target angiogenesis in women with endometriosis.

Endometriosis requires medical management during a woman's reproductive years. Most treatments aim to create a hypoestrogenic milieu, but for patients wishing to conceive, drugs that allow normal ovarian function are needed. Targeting angiogenesis, a hallmark of the disease, using dopamine agonists (DAs) is a promising strategy for endometriosis treatment.

The differential diagnoses of uterine leiomyomas and leiomyosarcomas using DNA and RNA sequencing.

Background: Although uterine leiomyomas and leiomyosarcomas are considered biologically unrelated tumors, they share morphologic and histologic characteristics that complicate their differential diagnosis. The long-term therapeutic option for leiomyoma is laparoscopic myomectomy with morcellation, particularly for patients who wish to preserve their fertility. However, because of the potential dissemination of undiagnosed or hidden leiomyosarcoma from morcellation, there is a need to develop a preoperative assessment of malignancy risk.