Perinatal outcomes are similar in programmed and modified natural frozen embryo transfer cycles.

Research Question: How do perinatal outcomes differ between programmed and modified natural frozen embryo transfer (FET) cycles?

Design: A retrospective cohort study of 839 patients was undertaken at a university-affiliated fertility practice undergoing single blastocyst FET cycles between 2014 and 2020. The primary outcome measures were the incidence of ischaemic placental disease, small for gestational age (SGA), intrauterine growth restriction (IUGR), preterm delivery, birth weight, and mode of delivery.

Results: When comparing programmed FET cycles with modified natural FET cycles, there was no increased risk of ischaemic placental disease [adjusted risk ratio (aRR) 0.

Venetoclax Induces BCL-2-Dependent Treg to TH17 Plasticity to Enhance the Antitumor Efficacy of Anti-PD-1 Checkpoint Blockade.

The specific BCL-2 small molecule inhibitor venetoclax induces apoptosis in a wide range of malignancies, which has led to rapid clinical expansion in its use alone and in combination with chemotherapy and immune-based therapies against a myriad of cancer types. While lymphocytes, and T cells in particular, rely heavily on BCL-2 for survival and function, the effects of small molecule blockade of the BCL-2 family on surviving immune cells is not fully understood. We aimed to better understand the effect of systemic treatment with venetoclax on regulatory T cells (Treg), which are relatively resistant to cell death induced by specific drugging of BCL-2 compared to other T cells.

Targeted Polymersome Delivery of a Stapled Peptide for Drugging the Tumor Protein p53:BCL-2-Family Axis in Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) remains a formidable diagnosis in need of new treatment paradigms. In this work, we elucidated an opportunity for therapeutic synergy in DLBCL by reactivating tumor protein p53 with a stapled peptide, ATSP-7041, thereby priming cells for apoptosis and enhancing their sensitivity to BCL-2 family modulation with a BH3-mimetic, ABT-263 (navitoclax). While this combination was highly effective at activating apoptosis in DLBCL , it was highly toxic , resulting in a prohibitively narrow therapeutic window.

Simulation-based training for embryo transfer for clinicians with differing levels of expertise: an application of the American Society for Reproductive Medicine Embryo Transfer Simulator.

Objective: To compare the learning curve of clinicians with different levels of embryo transfer (ET) experience using the American Society for Reproductive Medicine (ASRM) Embryo Transfer Simulator.

Design: Prospective cohort study.

Setting: Single large university-affiliated in vitro fertilization center.

Modified natural and optimized programmed frozen embryo transfers have equivalent live birth rates: an analysis of 6,682 cycles.

Objective: To compare the live birth rates (LBRs) in modified natural and programmed single blastocyst frozen embryo transfer (FET) cycles.

Design: Retrospective cohort study.

Setting: University-affiliated fertility practice.

Inhibition of FOXP3 by stapled alpha-helical peptides dampens regulatory T cell function.

Despite continuing advances in the development of novel cellular-, antibody-, and chemotherapeutic-based strategies to enhance immune reactivity, the presence of regulatory T cells (Treg cells) remains a complicating factor for their clinical efficacy. To overcome dosing limitations and off-target effects from antibody-based Treg cell deletional strategies or small molecule drugging, we investigated the ability of hydrocarbon stapled alpha-helical (SAH) peptides to target FOXP3, the master transcription factor regulator of Treg cell development, maintenance, and suppressive function. Using the crystal structure of the FOXP3 homodimer as a guide, we developed SAHs in the likeness of a portion of the native FOXP3 antiparallel coiled-coil homodimerization domain (SAH-FOXP3) to block this key FOXP3 protein-protein interaction (PPI) through molecular mimicry.

The effect of interpregnancy interval on preterm birth and low birth weight in singleton pregnancies conceived without assistance or by infertility treatments.

Objective: To determine the association of interpregnancy interval on perinatal outcomes and whether this was influenced by mode of conception.

Design: Retrospective cohort.

Setting: Centers for Disease Control and Prevention's natality national database.

Endometrial compaction does not predict live birth in single euploid frozen embryo transfers: a prospective study.

Study Question: Is there a relationship between endometrial compaction and live birth in euploid frozen embryo transfer (FET) cycles?

Summary Answer: Live birth rates (LBRs) were similar in both patients that demonstrated endometrial compaction or no compaction in single euploid FETs.

What Is Known Already: There has been increasing interest in the correlation between endometrial compaction and clinical outcomes but there has been conflicting evidence from prior investigations.

Study Design, Size, Duration: This was a prospective observational study from 1 September 2020 to 9 April 2021.

Placental pathology of term singleton live births conceived with fresh embryo transfer compared with those conceived without assisted reproductive technology.

Objective: To compare placental pathology from term singleton live births conceived with fresh embryo transfer vs. those conceived without assisted reproductive technology (ART).

Design: Retrospective cohort study.

The psychological impact of the coronavirus disease 2019 pandemic on women who become pregnant after receiving treatment for infertility: a longitudinal study.

Objective: To compare the impact of the coronavirus disease 2019 (COVID-19) pandemic on the psychological health of patients with infertility who have become pregnant with that of women who have not.

Design: Prospective cohort study conducted from April 2020 to June 2020. The participants completed three questionnaires over this period.

Multifoetal gestations mediate the effect of in vitro fertilisation (IVF) on ischaemic placental disease in autologous oocyte IVF more than donor oocyte IVF.

Background: Ischaemic placental disease (IPD) affects 16%-23% of pregnancies in the United States. In vitro fertilisation (IVF) is a risk factor for IPD, and the magnitude of increase in risk differs for individuals using donor oocytes (donor IVF) versus their own oocytes (autologous IVF). In addition, multifoetal gestations, which are more common in IVF than non-IVF pregnancies, also are a risk factor for IPD.

Venetoclax imparts distinct cell death sensitivity and adaptivity patterns in T cells.

BH3 mimetics are increasingly used as anti-cancer therapeutics either alone or in conjunction with other chemotherapies. However, mounting evidence has also demonstrated that BH3 mimetics modulate varied amounts of apoptotic signaling in healthy immune populations. In order to maximize their clinical potential, it will be essential to understand how BH3 mimetics affect discrete immune populations and to determine how BH3 mimetic pressure causes immune system adaptation.

Long-term reproductive outcomes in patients with unexplained infertility: follow-up of the Fast Track and Standard Treatment Trial participants.

Objective: To evaluate long-term reproductive outcomes in couples who were enrolled in a large randomized controlled trial that studied optimal treatment for unexplained infertility.

Design: Telephone survey, administered between March 2019 and February 2020.

Setting: Large urban university-affiliated fertility center.

Clinical outcomes and utilization from over a decade of planned oocyte cryopreservation.

Research Question: What is the clinical experience of patients who have undergone planned oocyte cryopreservation and oocyte thawing and warming?

Design: Retrospective observational cohort study. All women who completed planned oocyte cryopreservation at a single large university-affiliated fertility centre between June 2006 and October 2020 were identified, including the subset who returned to use their oocytes. Patients who underwent oocyte cryopreservation for medical reasons were excluded.

Employee benefit or occupational hazard? How employer coverage of egg freezing impacts reproductive decisions of graduate students.

Objective: To better understand if employer-based financial coverage of non-medical oocyte cryopreservation impacts the way women make decisions about their reproduction, including the decision to pursue oocyte cryopreservation and the time frame in which they plan to begin family building.

Design: Prospective survey study.

Setting: Academic medical center.

Low cryoprotectant concentration rapid vitrification of mouse oocytes and embryos.

Vitrification of mammalian oocytes and embryos is typically a two-step procedure involving two solutions of increasing concentrations of cryoprotectants. In the present study, we report a simple vitrification protocol that uses low cryoprotectant concentration and a single medium (LCSM). This medium, along with the traditional high concentration two media (HCTM) protocol, was used to vitrify mouse oocytes, zygotes, and blastocysts using silica capillary, cryotop, cryolock, and 0.

Placenta Accreta Spectrum: In Vitro Fertilization and Non-In Vitro Fertilization and Placenta Accreta Spectrum in a Massachusetts Cohort.

Objective: The incidence of placenta accreta spectrum (PAS) has been increasing in the United States. In addition, there has also been an increase in the utilization of in vitro fertilization (IVF). The IVF pregnancies confer an increased risk of adverse obstetric and neonatal outcomes, but there is limited data on whether IVF is associated with PAS.

Infertility remains a top stressor despite the COVID-19 pandemic.

Research Question: What is the psychological impact of the COVID-19 pandemic on infertility patients?

Design: An anonymous cross-sectional online survey was sent to patients who attended a large university-affiliated infertility practice in the USA between 1 January 2019 and 1 April 2020. At three different time-points respondents were asked to note their top three stressors, from a list of 10 commonly reported life stressors.

Results: The questionnaire was sent to 10,481 patients, with 3604 responses (response rate 34%) received.

Vanishing Twins Conceived Through Fresh In Vitro Fertilization: Obstetric Outcomes and Placental Pathology.

Objective: To characterize the obstetric outcomes and placental pathology in live births arising from vanishing twin pregnancies compared with nonreduced in vitro fertilization (IVF) pregnancies.

Methods: This is a retrospective cohort study of live births resulting from fresh embryo transfers after IVF cycles with autologous oocytes from 2004 through 2017 at a large academic fertility center. Clinical information and pathology reports were reviewed.

The importance of mediation in reproductive health studies.

A mediator is a factor that occurs after the exposure of interest, precedes the outcome of interest (i.e. between the exposure and the outcome) and is associated with both the exposure and the outcome of interest (i.

To test or not to test? A framework for counselling patients on preimplantation genetic testing for aneuploidy (PGT-A).

Study Question: What is the treatment path and cumulative live birth (CLB) rate from a single oocyte retrieval of patients who intend to pursue PGT-A at the start of an IVF cycle compared to matched controls?

Summary Answer: The choice of PGT-A at the start of the first IVF cycle decreases the CLB per oocyte retrieval for patients <38 years of age, however patients ≥38 years of age benefit significantly per embryo transfer (ET) when live birth (LB) is evaluated.

What Is Known Already: PGT-A has been shown to reduce the practice of transferring multiple embryos and to confer a higher live birth rate per transfer.

Study Design, Size, Duration: This is a retrospective cohort study from December 2014 to September 2016, involving 600 patients: those intending PGT-A for their first IVF cycle (N = 300) and their matched controls.

On-chip oocyte denudation from cumulus-oocyte complexes for assisted reproductive therapy.

Human infertility can be treated using assisted reproductive technology (ART) such as intracytoplasmic sperm injection (ICSI). But current ART techniques suffer from multiple cumbersome processes requiring technically skilled personnel. Microfluidics technologies offer unique opportunities to streamline ART procedures, reduce stress imposed upon gametes and embryos, and minimize the operator-to-operator variability.

The Environment and Reproductive Health (EARTH) Study: A Prospective Preconception Cohort.

Background: The Environment and Reproductive Health (EARTH) Study is an ongoing prospective preconception cohort designed to investigate the impact of environmental, nutritional, and lifestyle factors among both women and men on fertility and pregnancy outcomes.

Methods: The EARTH Study recruits women 18 to 45 years and men 18 to 55 years seeking fertility evaluation and treatment at the Massachusetts General Hospital (MGH) Fertility Center, Boston, USA. Women and men are eligible to join either independently or as a couple.