Kyung Eui Park

Effects of insulin-sensitizing agents and insulin resistance in women with polycystic ovary syndrome

Objective The aim of this study was to investigate the effect of insulin sensitizing agents on hormonal and metabolic parameters as well as menstrual patterns in women with polycystic ovary syndrome (PCOS). Methods One hundred and twenty-three patients with PCOS were included. Metformin was administered to patients at 1,500 mg or 1,700 mg daily for 3 months. If the patients had no improvement of the menstrual cycle or metformin-related adverse effects developed, the patients changed medication to a daily dose of either 15 mg pioglitazone or up to 45 mg. Then resumption of a regular menstrual cycle or recovery of ovulation was evaluated. Hormonal and metabolic profiles were compared between the response and non-response group to insulin sensitizing agents. Results One hundred and five patients with PCOS were treated with metformin for 3 months. Forty-eight patients (45.7%) showed improvement of menstrual cycle regularity after 3 months of metformin use, whereas 57 patients (54.3%) had no change. The mean free testosterone measured after 3 months of treatment was significantly lower in metformin responders than in non-responders. The other parameters did not differ between the groups. Of the 23 patients who used pioglitazone for 3 to 6 months, 19 patients (82.6%) showed improvement in their menstrual cycles. Conclusion Metformin treatment seems to be effective for the improvement of menstrual cyclicity irrespective of insulin resistance in women with PCOS. When metformin related adverse effect occurred, pioglitazone would be effective for aiding the resumption of the menstrual cycle.

Effects of Urinary and Recombinant Gonadotropins on In Vitro Maturation Outcomes of Mouse Preantral Follicles

Gonadotropins including follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play a crucial role in human-assisted reproduction techniques. Despite wide use of recombinant gonadotropins in clinical practice, the efficacy of urinary gonadotropins and the dosage of LH component have not yet been elucidated. This study was designed to investigate the difference of follicle culture outcomes according to various compositions of gonadotropins during in vitro culture of mouse preantral follicles. Ovaries were obtained from the 14-day-old C57BL/6 mice, and preantral follicles were isolated and cultured in culture media supplemented with human menopausal gonadotropin (hMG) 200 mIU/mL (group 1), recombinant FSH and LH (rFSH + rLH) 200 mIU/mL each (group 2), rFSH 200 mIU/mL + rLH 100 mIU/mL (group 3), or rFSH 200 mIU/mL + rLH 20 mIU/mL (group 4). Follicle survival rate was significantly lower in group 4. Antral follicles in lower doses of LH (groups 3, 4) showed a statistically significant larger diameter and tended to have a higher antral formation rate. However, follicles in group 1 tended to have a higher oocyte maturation rate. Estradiol concentration from conditioned media from 2:1 FSH/LH (group 3) was significantly higher than those from 1:1 FSH/LH (group 2) or 10:1 FSH/LH (group 4). Half dose of rLH to rFSH facilitated upregulation of growth differentiation factor 9 (Gdf9) expression in granulosa cells when compared to 1:1 FSH/LH or 10:1 FSH/LH. Conclusively, recombinant gonadotropins provided a comparable condition to hMG, and half dose of rLH to rFSH seems to be more suitable for follicular development during in vitro culture.

The expression profile of angiotensin system on thawed murine ovaries

Freezing and thawing is one of the most widely used tissue engineering techniques for the preservation of ovaries. Many cells and tissues demonstrate changes in functional gene expression after thawing. Several studies have reported the important roles of angiotensin (AT) system during the ovarian follicular growth. AT system consists of ATII, and ATII receptors type I (ATII-RI) and type II (ATII-RII). However, little is known whether frozen-thawed ovaries show any alteration of AT system member gene expression when treated with survival-enhancing factors. We aimed to investigate whether mass freezing and thawing with or without the use of Rho-associated kinase (ROCK) inhibitors up- or down-regulate the expression of ATII, ATII-RI, and ATII-RII genes on frozen-thawed ovarian tissues. Significant changes in the expression of ATII, ATII-RI, and ATII-RII genes were observed on thawed ovaries when compared to fresh control. The treatment with ROCK inhibitors did not significantly alter their expression. In conclusion, freezing and thawing of ovarian tissue may affect the mRNA expression levels of intra-ovarian AT system genes, and modulation of ROCK inhibitor activity may not regulate AT system on the frozenthawed ovarian tissue.

Effects of alginate hydrogels on in vitro maturation outcome of mouse preantral follicles

Ovarian follicle growth and oocyte maturation require communications between the oocyte and its surrounding somatic cells. Three-dimensional structures provide cell culture conditions that increase interactions between the cellular components when compared to 2-dimensional structures. In this study, alginate matrices were employed to maintain a 3-dimensional architecture to examine its effects on in vitro culture outcomes using mouse ovarian follicles. Ovaries were obtained from the 14-day-old C57BL/6 mice, and preantral follicles were isolated and cultured in either a 2-dimensional culture system or 0.125/0.25% alginate matrices-based 3-dimensional culture systems. We successfully observed encapsulation within 0.125 and 0.25% alginate matrices, which maintained the follicular spherical architecture, with a centrally placed oocyte and layers of granulosa cells. All culture outcomes were comparable between the 2-dimensional control and 3-dimensional alginate group. However, 0.25% alginate hydrogels led the lower rates of follicle survival and antral formation in comparison to the 2-dimensional control and 0.125% alginate. These results demonstrate that a non-permissive stiffness from the high concentration of alginate could interfere with cell-to-cell communication of oocytes and follicles. The extracellular matrix interacts with the oocyte and granulosa cells, resulting in direct effects on their proliferation. The development of a 3-dimensional culture system can enhance follicle maturation and produce meiotically-competent oocytes to provide advanced reproductive options for IVF patients in the future.

Effects of Estradiol on the Paracrine Regulator Expression of In Vitro Maturated Murine Ovarian Follicles

The preservation of female germ cells is important in the individuals with ovarian dysfunction and failure. For this purpose, ovarian follicle in vitro maturation (OFIVM) is an important technology for the retrieval of mature oocytes. In the in vivo follicular development, paracrine factors such as angiotensin (AT) and anti-Müllerian hormone (AMH) play important roles. We attempted to add estrogen during the OFIVM and to assess their expression on the follicular cells. The ovaries and pre-antral follicles were collected from 13-day C57BL/6 mice and cultured in vitro with estradiol (E2) treatment for up to two weeks. In the whole ovaries, the expression of AT II was decreased and the expression of AMH was similar between control and E2-treated ovaries after in vitro culture. Although there was no difference in the survival, ovulation, maturation and fertilization rates between control and E2-treated groups, the expression of AT II in the follicular cells was down-regulated after E2 treatment at mRNA level, and AMH showed similar expression. In conclusion, adding E2 in OFIVM may regulate paracrine factors and their receptors that are related to follicular development. Further investigations are necessary to elucidate the roles of various sex hormones in the regulation of AT and AMH expression during the OFIVM.

Vesicovaginal fistula following large-loop excision of the transformation zone in a chronic systemic glucocorticoid user.

A 42‐year‐old woman with a history of a large‐loop excision of transformation zone for cervical intraepithelial neoplasia III four years previously visited our outpatient department for cervical intraepithelial neoplasia I that newly detected by colposcopy‐directed punch biopsy. Her other medical conditions include systemic lupus erythematosus on daily prednisolone 15 mg during 19 years. After second large‐loop excision of transformation zone, delayed vesicovaginal fistula was confirmed by indigo carmine leakage test, computed tomography scan, and cystoscopy. Fistula was primarily repaired with indwelling double‐J catheters with anchoring omentum on suture site.

The Use of Tenaculum During Intrauterine Insemination May Not Affect the Pregnancy Outcome

Purpose The association between tenaculum application to the cervix just before embryo transfer and lower pregnancy rate has been reported. However, studies on the use of tenaculum in intrauterine insemination (IUI) cycles are not available. This study attempted to investigate whether the use of tenaculum affects the clinical outcomes of IUI. Materials and Methods Two hundred and thirty three CC/hMG/IUI cycles of one hundred and forty three couples were recruited at Seoul National University Hospital from October 2006 to December 2008. Mock insemination and IUI with or without tenaculum application to the cervix were also performed, and clinical pregnancy rate was compared. Results The incidence of difficult mock insemination at the beginning of cycle was higher in the tenaculum use group (p < 0.001). No significant statistical difference in the clinical pregnancy rate was observed between the groups with or without tenaculum application (12.1% vs. 18.5%; p = 0.175), which was not influenced by the difficulty of mock insemination. Conclusion The use of tenaculum during IUI may not affect the pregnancy outcome. Our results need to be confirmed by a prospective study in a larger population.

Early gonadotropin-releasing hormone antagonist protocol in women with polycystic ovary syndrome: A preliminary randomized trial

Objective To prospectively evaluate the efficacy and safety of a fixed early gonadotropin-releasing hormone (GnRH) antagonist protocol compared to a conventional midfollicular GnRH antagonist protocol and a long GnRH agonist protocol for in vitro fertilization (IVF) in patients with polycystic ovary syndrome (PCOS). Methods Randomized patients in all three groups (early antagonist, n=14; conventional antagonist, n=11; long agonist, n=11) received 21 days of oral contraceptive pill treatment prior to stimulation. The GnRH antagonist was initiated on the 1st day of stimulation in the early antagonist group and on the 6th day in the conventional antagonist group. The GnRH agonist was initiated on the 18th day of the preceding cycle. The primary endpoint was the number of oocytes retrieved, and the secondary endpoints included the rate of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and the clinical pregnancy rate. Results The median total number of oocytes was similar among the three groups (early, 16; conventional, 12; agonist, 19; p=0.111). The early GnRH antagonist protocol showed statistically non-significant associations with a higher clinical pregnancy rate (early, 50.0%; conventional, 11.1%; agonist, 22.2%; p=0.180) and lower incidence of moderate-to-severe OHSS (early, 7.7%; conventional, 18.2%; agonist, 27.3%; p=0.463), especially among subjects at high risk for OHSS (early, 12.5%; conventional, 40.0%; agonist, 50.0%; p=0.324). Conclusion In PCOS patients undergoing IVF, early administration of a GnRH antagonist may possibly lead to benefits due to a reduced incidence of moderate-to-severe OHSS in high-risk subjects with a better clinical pregnancy rate per embryo transfer. Further studies with more subjects are required.

An unusual presentation of obstructed hemivagina and ipsilateral renal anomaly syndrome: A case report

820 AN UNUSUAL PRESENTATION OF OBSTRUCTED HEMIVAGINA AND IPSILATERAL RENAL ANOMALY SYNDROME: A CASE REPORT Woo-Oh Kim, MD, Kyung Eui Park, MD, Seung-Yup Ku, MD, PhD, Seok Hyun Kim, MD, PhD, Young Min Choi, MD, PhD, Jung Gu Kim, MD, PhD, Shin Yong Moon, MD, PhD Department of Obstetrics and Gynecology, Seoul National University College of Medicine; Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, Korea