Compassionate embryo transfer: physician practices and perspectives.

OBJECTIVE: To assess reproductive endocrinology and infertility (REI) physicians' basic knowledge of compassionate embryo transfer, current practices, and perceived barriers to offering compassionate transfer. DESIGN: Cross-sectional survey study. SETTING: Not applicable. PATIENTS: Not applicable. INTERVENTION: None. MAIN OUTCOME MEASURES: Number of physicians offering and performing compassionate transfer, barriers, beliefs and demographics of physicians. RESULTS: A total of 744 members of the Society for Reproductive Endocrinology and Infertility were sent the survey, and 202 (27.1%) responded. Of the 168 (83.2%) physicians who had heard of compassionate transfer, 75 (44.6%) had offered it. In all, 130 physicians stated that they would offer compassionate transfer if there was patient demand, and 74 would offer it if there were American Society for Reproductive Medicine guidelines. Among physicians who did not offer compassionate transfer, 97 cited lack of patient interest as a barrier. In all, 55 physicians had performed compassionate transfer (range 0-8) performed within the past 2 years. The majority of physicians (76.4%) placed embryos in the endometrium, and there was no consensus on timing. Of the physicians, 27 restricted the number of embryos transferred. Three physicians reported pregnancies following compassionate transfer; none were ectopic. CONCLUSION: Data from this survey suggest that REI physicians have a wide range of knowledge and practices concerning compassionate transfer. Individual practices should be encouraged to develop written protocols regarding the use of embryos for nonreproductive purposes. American Society for Reproductive Medicine should develop recommendations to standardize the practice of compassionate transfer for those physicians who plan to offer this procedure.

GATA2 and Progesterone Receptor Interaction in Endometrial Stromal Cells Undergoing Decidualization.

The transcription factor GATA2 is important for endometrial stromal cell decidualization in early pregnancy. Progesterone receptor (PGR) is also critical during decidualization but its interaction with GATA2 in regulating genes and pathways necessary for decidualization in human endometrium are unclear. RNA-sequencing (RNA-seq) was performed to compare gene expression profiles (n = 3), and chromatin immunoprecipitation followed by sequencing (ChIP-seq) using an antibody against GATA2 (n = 2) was performed to examine binding to target genes in human endometrial stromal cells undergoing in vitro decidualization (IVD including estrogen, progestin, and 3',5'-cyclic AMP analogue) or vehicle treatment. We identified 1232 differentially expressed genes (DEGs) in IVD vs vehicle. GATA2 cistrome in IVD-treated cells was enriched with motifs for GATA, ATF, and JUN, and gene ontology analysis of GATA2 cistrome revealed pathways that regulate cholesterol storage, p38 mitogen-activated protein kinase, and the c-Jun N-terminal kinase cascades. Integration of RNA-seq and ChIP-seq data revealed that the PGR motif is highly enriched at GATA2 binding regions surrounding upregulated genes in IVD-treated cells. The integration of a mined public PGR cistrome in IVD-treated human endometrial cells with our GATA2 cistrome showed that GATA2 binding was significantly enhanced at PGR-binding regions in IVD vs vehicle. Interrogating 2 separate ChIP-seq data sets together with RNA-seq revealed integration of GATA2 and PGR action to coregulate biologic processes during decidualization of human endometrial stromal cells, specifically via WNT activation and stem cell differentiation pathways. These findings reveal the key pathways that are coactivated by GATA2 and PGR that may be therapeutic targets for supporting implantation and early pregnancy.

Endometriosis.

Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-ß. Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.