Follicular phase length is not related to live birth outcome in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination cycles in a multicenter trial.

Objective: To evaluate the effect of follicular phase length (FPL) on pregnancy outcomes and endometrial thickness (ET) among women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination (OS-IUI) with clomiphene citrate, letrozole, or gonadotropins.

Design: Cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation randomized controlled trial.

Setting: Multicenter randomized controlled trial.

Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRASG12C.

Unlabelled: Covalent inhibitors of KRASG12C have shown antitumor activity against advanced/metastatic KRASG12C-mutated cancers, though resistance emerges and additional strategies are needed to improve outcomes. JDQ443 is a structurally unique covalent inhibitor of GDP-bound KRASG12C that forms novel interactions with the switch II pocket. JDQ443 potently inhibits KRASG12C-driven cellular signaling and demonstrates selective antiproliferative activity in KRASG12C-mutated cell lines, including those with G12C/H95 double mutations.

GnRH receptor-activating autoantibodies in polycystic ovary syndrome: identification of functional epitopes and development of epitope mimetic inhibitors.

Purpose: We have recently demonstrated that gonadotrophin-releasing hormone receptor-activating autoantibodies (GnRHR-AAb) are associated with polycystic ovary syndrome (PCOS). The aim of this study was to map the antigenic epitopes of GnRHR-AAb from PCOS patients, and develop retro-inverso peptide inhibitors that specifically target GnRHR-AAb.

Methods: Serum samples from ten GnRHR-AAb-positive PCOS patients and ten GnRHR-AAb-negative healthy controls were tested.

Relationship between semen regurgitation and pregnancy rates with intrauterine insemination.

Objective: To evaluate the relationship between semen regurgitation and intrauterine insemination (IUI) outcomes. We hypothesized that clinical pregnancy rates and live birth rates would be reduced when regurgitation occurred.

Design: Retrospective cohort study.

Juvenile cystic adenomyoma, a rare diagnostic challenge: Case Reports and literature review.

Objective: To report 2 very rare cases of young women who presented with severe dysmenorrhea and a large cystic lesion in the myometrium, which presented a diagnostic dilemma because they were confused with a Müllerian anomaly.

Design: Case reports and a literature review.

Setting: A university-based reproductive endocrinology and infertility clinic in the United States.

Elevated activity levels of activating autoantibodies to the GnRH receptor in patients with polycystic ovary syndrome.

Objectives: 1) To confirm the correlation of GnRH receptor (GnRHR) activating autoantibody (AAb) activity with polycystic ovary syndrome (PCOS) diagnosis in large well defined cohorts; and 2) to evaluate suppression of AAb activity with GnRH antagonist medication in transfected GnRHR cells exposed to serum of PCOS patients.

Design: Cross-sectional matched case-control study.

Setting: University-based research facility.

Increased testosterone and proinflammatory cytokines in patients with polycystic ovary syndrome correlate with elevated GnRH receptor autoantibody activity assessed by a fluorescence resonance energy transfer-based bioassay.

Purpose: The recently identified agonistic autoantibodies (AAb) to the gonadotropin-releasing hormone receptor (GnRHR) are a novel investigative and therapeutic target for polycystic ovary syndrome (PCOS). In this study, we used a new cell-based fluorescence resonance energy transfer (FRET) bioassay to analyze serum GnRHR-AAb activity and examine its relationship with testosterone and proinflammatory cytokines in patients with PCOS.

Methods: Serum samples from 33 PCOS patients, 39 non-PCOS ovulatory infertile controls and 30 normal controls were tested for GnRHR-AAb activity and proinflammatory cytokines in a FRET-based bioassay and multiplex bead-based immunoassay, respectively.

CYP27A1-dependent anti-melanoma activity of limonoid natural products targets mitochondrial metabolism.

Three limonoid natural products with selective anti-proliferative activity against BRAF(V600E) and NRAS(Q61K)-mutation-dependent melanoma cell lines were identified. Differential transcriptome analysis revealed dependency of compound activity on expression of the mitochondrial cytochrome P450 oxidase CYP27A1, a transcriptional target of melanogenesis-associated transcription factor (MITF). We determined that CYP27A1 activity is necessary for the generation of a reactive metabolite that proceeds to inhibit cellular proliferation.

The Role of GnRH Receptor Autoantibodies in Polycystic Ovary Syndrome.

Objective: Is polycystic ovary syndrome (PCOS) associated with activating autoantibodies (AAb) to the second extracellular loop (ECL2) of gonadotropin-releasing hormone receptor (GnRHR)?

Design And Methods: We retrospectively screened sera from 40 patients with PCOS and 14 normal controls (NCs) with regular menses using enzyme-linked immunosorbent assay (ELISA) for the presence of GnRHR-ECL2-AAb. We obtained similar data from 40 non-PCOS ovulatory but infertile patients as a control group (OIC) of interest. We analyzed GnRHR-ECL2-AAb activity in purified immunoglobulin (Ig)G using a cell-based GnRHR bioassay.

Does the ultrasound appearance of the endometrium during treatment with assisted reproductive technologies influence pregnancy outcomes?

We evaluated endometrial pattern, defined as the relative echogenicity of the endometrium on a longitudinal uterine ultrasonic section, as a surrogate for endometrial receptivity in an attempt to evaluate the association between endometrial pattern and pregnancy outcome in women who underwent ART treatment. The primary outcome was live birth and secondary outcomes were clinical intrauterine pregnancy and miscarriage. Potential associations were evaluated using cluster-weighted generalized estimating equations to account for within-couple correlation among repeated ART cycles while adjusting for potentially confounding variables.

Risk of Ovarian Malignancy in Patients Undergoing Radical Cystectomy for Bladder Cancer.

Objective: To determine whether there is an increased risk of ovarian cancer in women undergoing radical cystectomy (RC) for bladder cancer using a large population-based data source. Current American Urologic Association guidelines suggest removal of ovaries during RC in women with bladder cancer, presumably to mitigate the risk ovarian cancer. However, recent data have demonstrated an increased risk of all-cause mortality, cardiovascular disease, osteoporosis, cognitive impairment, and diminished sexual function in some populations of women after oophorectomy.

Lipids and Women's Health: Recent Updates and Implications for Practice.

The obstetrician/gynecologist frequently serves as the primary care physician for women. Specialty-specific guidelines vary in screening recommendations for lipid disorders; women's health practitioners often follow recommendations to screen at age 45 in the absence of other risk factors. However, 2013 American College of Cardiology/American Heart Association cholesterol guidelines recommend screening at age 21 to capture those at risk of cardiovascular disease and allow for early intervention with lifestyle and, in the most severe cases, evidence-based statins.

Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.

In breast cancer, estrogen receptor alpha (ERα) positive cancer accounts for approximately 74% of all diagnoses, and in these settings, it is a primary driver of cell proliferation. Treatment of ERα positive breast cancer has long relied on endocrine therapies such as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders (SERDs). The steroid-based anti-estrogen fulvestrant (5), the only approved SERD, is effective in patients who have not previously been treated with endocrine therapy as well as in patients who have progressed after receiving other endocrine therapies.

The dilemma of counseling patients about poor prognosis: live birth after IVF with autologous oocytes in a 43-year-old woman with FSH levels above 30 mIU/mL.

Providing reasonable expectations to patients with diminished ovarian reserve prior to attempting pregnancy through in vitro fertilization (IVF) is one of the most challenging aspects of fertility care. In some instances, advice from the clinician to pursue more effective treatment, such as donor oocytes, may not be acceptable to the patient. In this case report, a patient is presented who represents a poor prognosis candidate for IVF treatment.

Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.

Tetrahydroisoquinoline 40 has been identified as a potent ERα antagonist and selective estrogen receptor degrader (SERD), exhibiting good oral bioavailability, antitumor efficacy, and SERD activity in vivo. We outline the discovery and chemical optimization of the THIQ scaffold leading to THIQ 40 and showcase the racemization of the scaffold, pharmacokinetic studies in preclinical species, and the in vivo efficacy of THIQ 40 in a MCF-7 human breast cancer xenograft model.

The effect of home exercise on ovulation induction using clomiphene citrate in overweight underserved women with polycystic ovarian syndrome.

Background: Age-adjusted rates of obesity are reported to be 35.8 % among US adult women and 49 % in some race/ethnicity, underserved populations. (1).

Developmentally delayed cleavage-stage embryos maintain comparable implantation rates in frozen embryo transfers.

Purpose: In fresh IVF cycles, embryos reaching the eight-cell stage on day 3 of development are thought to have a higher chance of implantation than those reaching this stage on day 4. To determine whether this difference persists after cryopreservation, we compared pregnancy and implantation rates between frozen embryo transfer (FET) cycles using delayed cleavage-stage embryos (cryopreserved day 4) and normal cleavage-stage embryos (cryopreserved day 3).

Methods: Participants underwent FET between 2008 and 2012 using embryos cryopreserved on either day 3 (n = 76) or day 4 (n = 48), depending on the length of time needed to achieve the eight-cell stage.

Can highly sensitive antimüllerian hormone testing predict failed response to ovarian stimulation?

Objective: To determine whether a newer commercially available antimüllerian hormone (AMH) enzyme-linked immunosorbent assay (picoAMH ELISA, AnshLabs) with a lower threshold of detection is predictive of successful ovarian stimulation in a population of women with diminished ovarian reserve (DOR).

Design: Retrospective case-control study.

Setting: University-based IVF program.

Cryopreserved embryo transfer: endometrial preparation and timing.

The objective of this article was to review and synthesize information from the scientific literature pertaining to the preparation of endometrium for cryopreserved embryo transfer. This article is a critical review of selected scientific literature, synthesis, and formulation of opinion. Estrogen and progesterone are necessary and sufficient to induce endometrial receptivity in cryopreserved embryo transfer cycles.

Enantioselective synthesis of highly substituted furans by a copper(II)-catalyzed cycloisomerization-indole addition reaction.

A catalytic enantioselective reaction based on a copper(II) catalyst strictly containing chiral anionic ligands is described. In the present work, copper(II)-phosphate catalyst promotes the intramolecular heterocyclization of 2-(1-alkynyl)-2-alkene-1-ones and facilitates high levels of enantioselectivity in the subsequent nucleophile attack. Mechanistic studies suggest that formation of a copper(II)-indole species is important for catalysis.

Risk of cervical intraepithelial neoplasia 2+ among women with a history of previous treatment for cervical intraepithelial neoplasia: ASCUS and LSIL Pap smears after treatment.

Objective: The objective of the current study was to describe outcomes among women with low-grade abnormalities on cervical cytology screening in the setting of previous excisional or ablative treatment for cervical intraepithelial neoplasia (CIN).

Methods: Study participants were recruited into the Study to Understand Cervical Cancer Early Endpoints and Determinants. At enrollment, the patient's previous cytology results, previous colposcopic biopsy results, and previous cervical procedures were recorded.

Asymmetric 1,4-dihydroxylation of 1,3-dienes by catalytic enantioselective diboration.

Asymmetric 1,4-dihydroxylations of 1,3-dienes, and other transformations, are initiated by the Pt-catalyzed enantioselective addition of bis(pinacolato)diboron (B(2)(pin)(2)) to conjugated dienes. The studies reported in this communication suggest that both cyclic and acyclic substrates will participate in this reaction; however, dienes which are unable to adopt the S-cis conformation are unreactive. For most substrates, 1,4-addition is the predominant pathway.