Risks of nonchromosomal birth defects, small-for-gestational age birthweight, and prematurity with in vitro fertilization: effect of number of embryos transferred and plurality at conception versus at birth.

Purpose: Excess embryos transferred (ET) (> plurality at birth) and fetal heartbeats (FHB) at 6 weeks' gestation are associated with reductions in birthweight and gestation, but prior studies have been limited by small sample sizes and limited IVF data. This analysis evaluated associations between excess ET, excess FHB, and adverse perinatal outcomes, including the risk of nonchromosomal birth defects.

Methods: Live births conceived via IVF from Massachusetts, New York, North Carolina, and Texas included 138,435 children born 2004-2013 (Texas), 2004-2016 (Massachusetts and North Carolina), and 2004-2017 (New York) were classified by ET and FHB.

The risk of birth defects with conception by ART.

Study Question: What is the association between ART conception and treatment parameters and the risk of birth defects?

Summary Answer: Compared to naturally conceived singleton infants, the risk of a major nonchromosomal defect among ART singletons conceived with autologous oocytes and fresh embryos without use of ICSI was increased by 18%, with increases of 42% and 30% for use of ICSI with and without male factor diagnosis, respectively.

What Is Known Already: Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects but have been limited by small sample size and inadequate statistical power, failure to differentiate results by plurality, differences in birth defect definitions and methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved.

Study Design, Size, Duration: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2015 that resulted in live births from 1 September 2004 to 31 December 2016 in Massachusetts and North Carolina and from 1 September 2004 to 31 December 2015 for Texas and New York: these were large and ethnically diverse States, with birth defect registries utilizing the same case definitions and data collected, and with high numbers of ART births annually.

Assessment of Birth Defects and Cancer Risk in Children Conceived via In Vitro Fertilization in the US.

Importance: Children with birth defects have a greater risk of developing cancer, but this association has not yet been evaluated in children conceived with in vitro fertilization (IVF).

Objective: To assess whether the association between birth defects and cancer is greater in children conceived via IVF compared with children conceived naturally.

Design, Setting, And Participants: This cohort study of live births, birth defects, and cancer from Massachusetts, New York, North Carolina, and Texas included 1 000 639 children born to fertile women and 52 776 children conceived via IVF (using autologous oocytes and fresh embryos) during 2004-2016 in Massachusetts and North Carolina, 2004-2015 in New York, and 2004-2013 in Texas.

Limits of current male fertility testing.

In the current approach to male fertility testing, basic semen analysis has limitations as a predictor of fertility status, and the technology is fraught with variability. Nonetheless, it remains the cornerstone of the evaluation of the male infertility, and we recommend adherence to most recent World Health Organization guidelines. Although the current sperm function tests (bioassays) have important drawbacks, they are still valuable as research tools.

Clinical outcomes following ICSI cycles using surgically recovered sperm and the impact of maternal age: 2004-2015 SART CORS registry.

Purpose: The aims of this study were (1) to evaluate clinical outcomes after ICSI cycles using surgically recovered sperm and (2) to assess the influence of maternal age on those outcomes.

Methods: A retrospective cohort study of 24,763 IVF cycles of fresh autologous oocytes and ICSI using surgically recovered sperm reported to the SART CORS database from 2004 to 2015.

Results And Conclusions: Older women had significantly longer stimulation (p < 0.

Alterations in expression of endometrial milk fat globule-EGF factor 8 (MFG-E8) and leukemia inhibitory factor (LIF) in patients with infertility and endometriosis.

Objective: The aim of this study was to compare the endometrial expression of milk fat globule-EGF factor 8 (MFG-E8), its receptor integrin αvβ3, and leukemia inhibitory factor (LIF) in patients with endometriosis and infertility and in healthy fertile patients during the window of implantation.

Methods: Five patients with peritoneal endometriosis and infertility (case group) and four healthy fertile patients (control group) were recruited. All patients were either diagnosed with or ruled out for endometriosis by laparoscopic surgery; the case group underwent surgery for infertility investigation and the control group for tubal ligation.

MFGE8 regulates TGF-β-induced epithelial mesenchymal transition in endometrial epithelial cells in vitro.

This study investigated the role of milk fat globule-epidermal growth factor-factor 8 (MFGE8) in TGF-β-induced epithelial-mesenchymal transition (EMT) of endometrial epithelial cells. These were in vitro studies using human endometrial epithelial cells and mouse blastocysts. We investigated the ability of TGF-β to induce EMT in endometrial epithelial cells (HEC-1A) by assessment of cytological phenotype (by light and atomic force microscopy), changes in expression of the markers of cell adhesion/differentiation E- and N-cadherin, and of the transcription factor Snail (by immunofluorescence and immunoblotting), and competence to support embryo attachment in a mouse blastocyst outgrowth assay.

ICSI outcomes in men undergoing TESE for azoospermia and impact of maternal age.

This retrospective study compared clinical outcomes in men with obstructive and nonobstructive azoospermia after ICSI following testicular sperm extraction and the influence of maternal age. Fertilisation rates, embryo quality, pregnancy rates, miscarriage rates and live birth rates were evaluated. Men with obstructive azoospermia (OA) had significantly higher rates of diploid fertilisation and clinical pregnancy than men with nonobstructive azoospermia (NOA), but miscarriage rates and live birth rates were not significantly different.

Predictive factors for ovarian response in a corifollitropin alfa/GnRH antagonist protocol for controlled ovarian stimulation in IVF/ICSI cycles.

Background: This secondary analysis aimed to identify predictors of low (<6 oocytes retrieved) and high ovarian response (>18 oocytes retrieved) in IVF patients undergoing controlled ovarian stimulation with corifollitropin alfa in a gonadotropin-releasing hormone (GnRH) antagonist protocol.

Methods: Statistical model building for high and low ovarian response was based on the 150 μg corifollitropin alfa treatment group of the Pursue trial in infertile women aged 35-42 years (n = 694).

Results: Multivariable logistic regression models were constructed in a stepwise fashion (P <0.

Transcriptome of early embryonic invasion at implantation sites in a murine model.

Successful implantation relies on the interaction between a competent embryo and a receptive endometrium. The aim of the present study was to investigate genes differentially expressed in early invasive embryonic tissue versus decidual tissue in mice. Samples were obtained from the ectoplacental cone, the immediately surrounding deciduas and from deciduas from interimplantation sites.

Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro.

Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear.

Impact of serum estradiol levels on the implantation rate of cleavage stage cryopreserved-thawed embryos transferred in programmed cycles with exogenous hormonal replacement.

Purpose: To investigate the impact of late follicular phase serum estradiol (E2) levels on implantation and pregnancy outcomes of cleavage stage cryopreserved/thawed embryos transferred in programmed cycles with exogenous hormonal replacement.

Methods: Retrospective cohort analysis of IVF patients with transfer of cryopreserved-thawed day-3 embryos in E2 and progesterone (P4) supplemented cycles (n = 208 cycles).

Main Outcome Measures: implantation and pregnancy rates according to late follicular phase serum E2 levels and early secretory phase E2/P4 ratios.

Endometriosis may be associated with mitochondrial dysfunction in cumulus cells from subjects undergoing in vitro fertilization-intracytoplasmic sperm injection, as reflected by decreased adenosine triphosphate production.

Objective: To determine whether endometriosis is associated with mitochondrial dysfunction in cumulus (granulosa [GC]) cells of subjects undergoing IVF-intracytoplasmic sperm injection (ICSI).

Design: Prospective cohort study.

Setting: An IVF clinic in a tertiary academic care center.

Sperm functional tests.

Several semen parameters are used to discriminate the fertile male from the subfertile male. The most widely used parameters are sperm concentration, motility, progressive motility, and sperm morphology. Semen analysis is usually applied as described in the World Health Organization manual for semen analysis.

Antimüllerian hormone regulates stem cell factor expression in human granulosa cells.

Objective: To determine whether there is a correlation between antimüllerian hormone (AMH) and stem cell factor (SCF) in serum, follicular fluid (FF), and granulosa cells (GCs), and to investigate a possible regulatory mechanism of AMH on SCF in human granulosa cells.

Design: Prospective clinical and experimental study.

Setting: Academic center.

Characterization of secreted proteins of 2-cell mouse embryos cultured in vitro to the blastocyst stage with and without protein supplementation.

Purpose: To identify the secreted proteins of murine embryos grown in vitro.

Methods: Two-cell mouse embryos (n=432) were randomly allocated to culture to the blastocyst stage in protein-free and in protein-supplemented (3 % BSA) media. Proteins were separated by SDS-PAGE; bands were visualized by coomassie staining, followed by in-gel trypsin digestion and liquid chromatography-tandem mass spectrometry.

Role for the endometrial epithelial protein MFG-E8 and its receptor integrin αvβ3 in human implantation: results of an in vitro trophoblast attachment study using established human cell lines.

Objective: To investigate the role of MFG-E8 and its receptor integrin αvβ3 in the attachment of trophoblast cells to the endometrial epithelium.

Design: Experimental in vitro study.

Setting: Academic center.

Tumor necrosis factor α up-regulates endometrial milk fat globule-epidermal growth factor 8 protein production via nuclear factor κB activation, resulting in cell migration of epithelial cells.

Objective: To explore the role of tumor necrosis factor (TNF) α, an early embryonic product, on endometrial epithelial cell migration and endometrial milk fat globule-epidermal growth factor 8 protein (MFG-E8) production.

Design: In vitro study.

Setting: Academic center.

Sex steroids regulate epithelial-stromal cell cross talk and trophoblast attachment invasion in a three-dimensional human endometrial culture system.

Human embryo implantation involves a complex network of molecular signaling that is modulated by endocrine and paracrine pathways. Here, we performed studies using a unique and recently developed three-dimensional (3D) implantation model, characterized by an endometrium-like 3D culture system and Jar cell-derived spheroids mimicking the embryo/trophoblast. The aims were to investigate the effects of 17β estradiol (E2) and medroxyprogesterone acetate (MPA) on (1) the interaction between epithelial and stromal cells, and (2) the attachment and invasion of trophoblast cells.

Modulation of the expression of the transcription factors T-bet and GATA-3 in immortalized human endometrial stromal cells (HESCs) by sex steroid hormones and cAMP.

T-bet and GATA-3 are known to regulate cytokine expression in T lymphocytes, and cytokines have been implicated in endometrial regulation and implantation. Previous work showed that female steroid hormones modulate the expression of T-bet in endometrial epithelial cells, suggesting a mechanism for local immune regulation in the human endometrium. We hypothesized that stromal cells are involved in immune regulation, as they have been shown to exert paracrine effects on other endometrial cells and compartments and also secrete cytokines.