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

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.

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.

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 insulin-sensitizing agents and insulin resistance in women with polycystic ovary syndrome / 대한생식의학회지

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.

Successful birth with preimplantation genetic diagnosis using single-cell allele-specific PCR and sequencing in a woman with hypochondroplasia due to FGFR3 mutation (c.1620C>A, p.N540K) / 대한생식의학회지

Hypochondroplasia (HCH) is an autosomal dominant inherited skeletal dysplasia, usually caused by a heterozygous mutation in the fibroblast growth factor receptor 3 gene (FGFR3). A 27-year-old HCH woman with a history of two consecutive abortions of HCH-affected fetuses visited our clinic for preimplantation genetic diagnosis (PGD). We confirmed the mutation in the proband (FGFR3:c.1620C>A, p.N540K), and established a nested allele-specific PCR and sequence analysis for PGD using single lymphocyte cells. We performed this molecular genetic analysis to detect the presence of mutation among 20 blastomeres from 18 different embryos, and selected 9 embryos with the wild-type sequence (FGFR3:c.1620C). A successful pregnancy was achieved through a frozen-thawed cycle and resulted in the full-term birth of a normal neonate. To the best of our knowledge, this is the first report of a successful pregnancy and birth using single-cell allele-specific PCR and sequencing for PGD in an HCH patient.

The Relationship between Wnt Antagonist Genes Polymorphisms and Changes in Production of Osteoprotegerin and Soluble Receptor Activator of NF-kB by Whole Blood Cells after Hormone Therapy / 대한골다공증학회지

OBJECTIVES: To investigate the relationship between single nucleotide polymorphism (SNP)s in Wnt antagonist genes, and production of osteoprotegerin (OPG) and soluble receptor activator of NF-kappaB ligand (sRANKL) by whole blood cells after hormone therapy (HT) in postmenopausal Korean women. MATERIALS AND METHODS: The Dkk1 c.318A>G, Dkk2 c.437G>A, Dkk3 c.1003A>G polymorphisms and sFRP3 c.970C>G, sFRP4 c.958C>A, and c.1019G>A polymorphisms, and sFRP5 c.20G>C polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), direct sequencing, and Taqman assay in 75 postmenopausal Korean women receiving estrogen-progestogen therapy. The production of OPG and sRANKL by lipopolysaccharide-stimulated whole blood cells (WBC) before and after HT of 6 months were also measured. RESULTS: Changes in the production of OPG and sRANKL by lipopolysaccharide-stimulated WBC, and in ratios of sRANKL(x1,000)/OPG after HT of 6 months were not different according to SNPs in Wnt signal pathway genes except Dkk1 c.318A>G SNP. The AA genotype of Dkk1 c.318A>G SNP showed significantly higher changes (pA, and c.1019G>A polymorphisms after HT. CONCLUSIONS: Dkk1 c.318A>G SNP are related with changes in ratios of sRANKL(x1,000)/OPG in terms of the production of OPG and sRANKL by lipopolysaccharide-stimulated whole blood cells after HT.

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.

The efficacy of a real-time optoelectronic device as a diagnostic tool of over cervical intraepithelial neoplasia 1 lesion / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to evaluate the sensitivity, specificity and accuracy of a real-time optoelectronic device (TruScreen) as a diagnostic tool of cervical intraepithelial neoplasia (CIN) or cervical cancer. METHODS: Two hundred ninety two patients who had been presented with previously abnormal Papanicolaou (Pap) smear or abnormal colposcopic findings between February 2009 and September 2009 were analyzed. The sensitivities, specificities and accuracies of TruScreen and liquid-based cytology were evaluated. RESULTS: As a diagnostic tool of CIN, carcinoma in situ (CIS), and cervical cancer, TruScreen appeared sensitive enough compared with liquid-based cytology (82.8% vs 75.9%), but the difference is statistically not significant (P=0.687). Specificity and accuracy of TruScreen were similar to those of liquid-based cytology (specificity 81.4% vs 83.3%, accuracy 81.5% vs 82.5%). CONCLUSION: The present study suggests that the TruScreen could be an option as a tool of screening test in CIN, CIS, and cervical cancer and also be used combined with Pap smear.