Jin Hyun Jun

Transcriptional profiling with a pathway-oriented analysis identifies dysregulated molecular phenotypes in the endometrium of patients with polycystic ovary syndrome.

CONTEXT Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligo/anovulation, hyperandrogenemia, infertility, and metabolic alterations related to insulin resistance. These abnormalities in PCOS may have complex effects on pathophysiology of the endometrium, contributing to infertility and endometrial disorders. OBJECTIVE The objective of this study was to examine dysregulated signaling pathways in the endometrium of patients with PCOS (PCOSE) by analyzing expression profiles with a pathway-oriented method. DESIGN Microarrays, RT-PCR, laser capture microdissection, and immunohistochemistry were performed with endometrial tissues. SETTING This study was performed at a university hospital laboratory. PATIENTS This study comprised 12 regularly cycling women and 12 PCOS patients. MAIN OUTCOME MEASURE Dysregulated signaling pathways in PCOSE were identified as a gene set. RESULTS Hierarchical clustering revealed distinct expression profiles for PCOSE and the endometrium of normal cycling women. Gene sets associated with androgen signaling were not enriched in PCOSE, although they affect ovarian physiology of PCOS patients. Several biological pathways including cell cycle, apoptosis, glycolysis, and integrin-Rho-cytoskeleton network were aberrantly down-regulated in PCOSE. Expression of genes constituting these gene sets enriched in normal cycling women was systemically down-regulated in PCOSE. Laser capture microdissection-coupled real-time RT-PCR and immunohistochemistry further demonstrated that cell proliferation in the stroma, but not the epithelium, is significantly reduced in PCOSE. CONCLUSIONS Systemic down-regulation of various signaling pathways in PCOSE with extremely prolonged proliferative phase provides insight into the abnormal phenotypes that reflect pathophysiology of PCOS in the endometrium, possibly leading to increased risks of endometrial disorders.

Efficacy of microsurgical epididymal sperm aspiration (MESA) and intracytoplasmic sperm injection (ICSI) in obstructive azoospermia

AbstractPurpose: Our purpose was to test whether micromanipulation using subzonal insemination and intracytoplasmic sperm injection could improve the poor fertilization and pregnancy rates obtained when attempting in vitro fertilization in patients with congenital absence of the vas deferens and unreconstructable obstructive azoospermia with microsurgically retrieved epididymal spermatozoa. Results: Conventional in vitro fertilization (group A; 14 cycles), subzonal insemination (group B; 13 cycles), and intracytoplasmic sperm injection (group C; 28 cycles) were carried out in 55 treatment cycles. Fertilization rates for groups A, B, and C were 16.1, 31.4, and 48.6%, respectively (P<0.05). Clinical pregnancy rates for groups A, B, and C were 7.1, 7.7, and 32.1% (P<0.05), respectively. In five cycles, intracytoplasmic sperm injection using epididymal sperm from alloplastic spermatoceles was performed and two clinical pregnancies (40%) were obtained. Conclusions: The combined microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection procedure is highly effective in improving the fertilization and pregnancy rate in congenital absence of the vas deferens and unreconstructable obstructive azoospermia. Furthermore, alloplastic spermatoceles may be useful for repeat sperm aspirations.