Seung-Yup Ku

Relations between interleukin-1, its receptor antagonist gene polymorphism, and bone mineral density in postmenopausal Korean women

We investigated the relation between polymorphisms in the interleukin-1(IL-1) and IL-1 receptor antagonist (IL-1ra) gene, and bone mineral density (BMD) in postmenopausal Korean women. The IL-1α C−889T polymorphism, and IL-1β C−511T polymorphism were examined by restriction fragment length polymorphism, and 86-bp variable number tandem repeat polymorphism in the IL-1ra gene was analyzed by the polymerase chain reaction and electrophoresis in 202 postmenopausal Korean women. Serum osteocalcin, and C-telopeptide of type I collagen were measured using a radioimmunoassay and enzyme-linked immunosorbent assay, respectively. BMD at the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometer. No significant differences in BMD or in serum bone markers levels were noted across the IL-1α or IL-1β genotype. There were no significant differences in the distribution of IL-1α or IL-1β genotype according to the status of bone mass. BMD in women carrying the A2 allele of the IL-1ra gene was significantly lower than those without this allele, and the A2 allele was more frequent in osteoporotic women than in normal women. These data suggest that IL-1ra gene VNTR polymorphism is a genetic factor that may affect BMD in Korean women.

Relationships between the insulin-like growth factor I (IGF-I) receptor gene G3174A polymorphism, serum IGF-I levels, and bone mineral density in postmenopausal Korean women

We investigated the relationships between the IGF-I receptor gene G3174A polymorphism, serum IGF-I levels, and bone mineral density (BMD) in postmenopausal Korean women. The IGF-I receptor gene G3174A polymorphism was analyzed in 367 postmenopausal Korean women. Serum levels of IGF-I, bone turnover markers (osteocalcin, bone alkaline phosphatase, carboxy-terminal cross-linking telopeptide of type I collagen), and BMD at the lumbar spine and proximal femur were measured. The frequencies of the AA, GA, and GG genotypes were 10.9%, 44.1%, and 45.0%, respectively. BMD at the lumbar spine was significantly higher for the AA genotype than the other genotypes and showed an A allelic dose effect; however, no significant differences in BMD were observed at the proximal femur with respect to genotype. No differences were noted between the three genotypes in terms of serum levels of IGF-I or bone turnover markers. Women with low BMD showed a lower prevalence of the AA genotype and A allele than age-matched women with normal BMD. Women with the AA genotype were found to have about half the risk of a low BMD than women with other genotypes. In conclusion, IGF-I receptor gene G3174A polymorphism is associated with lumbar spine BMD in postmenopausal Korean women.

Gonadotropin ratio affects the in vitro growth of rhesus ovarian preantral follicles

In vitro follicle growth (IVFG) strategy is critical in the fertility preservation of cancer survivors; however, its optimal protocol needs to be developed using primate models since the availability of human samples is limited. Only a few previous studies have reported the successful IVFG of rhesus monkey ovaries using low-dose follicle-stimulating hormone (FSH) (0.3 or 3u2005ng/mL) and long-term culture (up to 5u2005weeks) and it is still uncertain in regard to the optimal culture duration and effective dose of treated gonadotropins applicable to the IVFG of rhesus preantral follicles. Recently, we have reported that the FSH to luteinizing hormone (LH) ratio affects the in vitro growth of murine ovarian follicles. We aimed to investigate whether gonadotropin ratios affect the efficiency of rhesus follicular growth in vitro. Ovaries were collected from six necropsied rhesus macaques (4–9u2005years) and preantral follicles were retrieved and cultured for 14u2005days using 200u2005mIU/mL FSH. The characteristics of follicular growth were compared between the FSH:LH=1:1 (n=24) and FSH:LH=2:1 (n=24) groups. High concentration gonadotropin treatment shortened the duration required for in vitro maturation of rhesus preantral follicles. The FSH:LH=2:1 group showed a faster follicular growth and enabled the acquisition of mature oocytes, although the expression of growth differentiation factor (GDF)-9 and anti-Müllerian hormone (AMH) did not differ significantly between the two groups. Taken together, high dose gonadotropin treatment can shorten the duration of IVFG and the gonadotropin ratio is important in the IVFG of rhesus monkey ovaries.

Induction of multiple ovulation via modulation of angiotensin II receptors in in vitro ovarian follicle culture models

In vitro culture of ovarian follicles is a promising bioengineering technique for retrieving fertilizable oocytes from preserved ovarian tissues of cancer survivors. However, current in vitro follicle culture techniques are labour‐intensive and of low efficiency, as only single follicle culture (SFC) has been possible to date. The present study investigated the feasibility of multifollicular cluster culture (MFCC) system using angiotensin II receptor (ATII‐Rc) analogues. Ovarian pre‐antral follicles isolated from 2‐week‐old C57BL6 mice were cultured with ATII‐Rc agonist or antagonist and their maturation outcomes were compared with control group. When single follicles were cultured, the ovulation and maturation rates were similar in all three groups. When three‐follicle clusters were cultured, up to three follicles were ovulated in the ATII‐Rc agonist group while none or one follicle ovulated in control or antagonist groups (p < 0.0001). Significantly higher numbers of mature oocytes were obtained in the agonist group (three‐follicle 28.2 ± 4.9 vs. SFC 11.0 ± 1.3, per 25 cultured droplets) (p < 0.0001), and the development of each fertilized oocytes was comparable to those from SFC. It is therefore concluded that this novel MFCC system can significantly improve the efficiency of in vitro mature oocyte retrieval via ATII‐Rc modulation. Copyright

Association between polymorphisms in period genes and bone density in postmenopausal Korean women

Abstract Objective In the present study, we aimed to investigate the association between genetic polymorphisms in period (PER) genes and bone mineral density (BMD) in postmenopausal Korean women. Methods The PER1 c.2247C> T and c.2884C> G polymorphisms; the PER2 c.661G> A and c.3731G> A polymorphisms; the PER3 c.2592G> A, c.3029C> T, c.3035C> T, and c.3083T> C polymorphisms, and the 54 bp variable number tandem repeats polymorphism were analyzed in 551 postmenopausal Korean women. Serum leptin, soluble leptin receptor, osteoprotegerin, soluble receptor activator of the nuclear factor-κB ligand, and bone markers including bone alkaline phosphatase and carboxy-terminal telopeptide of type I collagen were measured, and the lumbar spine and femoral neck BMDs were also determined. Results The PER2 c.661G> A, PER3 c.3029C> T and c.3035C> T polymorphisms were not observed. The PER2 and PER3 polymorphisms evaluated were not related to BMD, whereas associations of the c.2247C> T and c.2884C> G polymorphisms in PER1 with the lumbar spine BMD were observed both singly and in combination. The CC haplotype homozygotes showed significantly lower lumbar spine BMD than participants with other genotypes. Additionally, 2.01-fold higher odds for osteoporosis of the lumbar spine were found in the CC haplotype homozygotes compared to women not carrying the haplotype CC allele. No significant differences in bone markers were detected according to the PER1 haplotype genotype. Conclusions Our results suggest that both the PER1 c.2247C> T and c.2884C> G polymorphisms may be genetic factors affecting the lumbar spine BMD in postmenopausal Korean women.

Indications of intrauterine insemination for male and non-male factor infertility.

Intrauterine insemination (IUI) is a widely used fertility treatment for couples with male and/or non-male factor infertility and is a relatively simple and inexpensive procedure. When used for unexplained infertility, IUI combined with ovarian stimulation increases the pregnancy rates, but evidence does not support this to be true when applied for male factor infertility. Recently, the revised World Health Organization laboratory manual for semen criteria provided a new insight for practical guidelines. Further randomized, controlled studies are necessary to develop standardized IUI strategies. The authors reviewed, via literature search, on the indications, prognostic factors, ovarian stimulation protocols, and methods that have been employed for IUI treatment.

Association between hormone therapy and nerve conduction study parameters in postmenopausal women

Objectiveu2003We aimed to analyze the association between hormone therapy (HT) and nerve conduction parameters. Methodsu2003This retrospective study consisted of 46 postmenopausal women not receiving HT, and 18 postmenopausal women who received HT. Eligible patients were identified from the hospitals database and the nerve conduction study was performed on the upper or lower limb without pain or other symptoms. Resultsu2003No significant difference was demonstrated in the unadjusted nerve conduction parameters according to HT. After adjusting for age and body mass index, the latency of the posterior tibial motor nerve in postmenopausal women receiving HT was significantly shorter than that in women not receiving HT. Moreover, the velocity of the median motor nerve tended to be faster in postmenopausal women receiving HT than those not receiving HT, although the difference was not statistically significant. Conclusionu2003These findings imply that HT may affect the nerve conduction parameters in postmenopausal women.

A successful live birth with in vitro fertilization and thawed embryo transfer after conservative treatment of recurrent endometrial cancer

Abstract Estrogen-dependent early stage endometrial cancer is relatively common in young women of reproductive age. The standard treatment is hysterectomy and bilateral salpingo-oophorectomy (BSO), even in early stage well-differentiated endometrial cancer patients. This surgical option results in permanent loss of fertility. There have been some reports of live births using in vitro fertilization after conservative management of endometrial cancer with high-dose progestin for the purpose of fertility preservation. However, most were not recurrent cases and pregnancy was achieved through conventional in vitro fertilization, which usually raises serum estradiol levels and may lead to the recurrence of endometrial cancer. To date, it is hard to find a case that can be referred for any possible different approach needed for the patients who experience recurrence. Here we report a successful live birth with in vitro fertilization using letrozole to maintain physiological levels of estradiol, and subsequent thawed embryo transfer after elective cryopreservation of embryos in a patient with recurrent endometrial cancer. There has been no evidence of disease recurrence at one year after delivery.

Feature of amenorrhea in postoperative tamoxifen users with breast cancer

Objective Tamoxifen has been used to prevent the recurrence of breast cancer. However, tamoxifen-users frequently experience amenorrhea and it can be confused from that caused by other hormonal abnormalities. In amenorrheic patients without breast cancer, clinicians usually measure the sex hormone levels that are known to be associated with ovarian or menstrual function. This study aimed to investigate the feature of female sex hormones in premenopausal breast cancer patients undergoing tamoxifen treatment. Methods The medical records of fifty-nine premenopausal breast cancer patients who underwent tamoxifen treatment were reviewed retrospectively. The study population consisted of amenorrheic patients (n=36) and patients with menstruation (n=23). Serum hormone levels were measured either specifically between cycle days 2 and 5 in menstruating patients or at any time in amenorrheic participants. Results Serum levels of lutenizing hormone and estradiol were not statistically different according to the presence of menstruation. Serum follicle stimulating hormone level was significantly higher in amenorrheic patients (8.1±5.7 mIU/mL) than those in menstruating subjects (5.1±2.2 mIU/mL) (p=0.01). Serum concentration of thyroid stimulating hormone was lower in patients with amenorrhea (1.5±0.9 vs. 2.3±2.2 μIU/mL, p=0.04), although the prevalence of hypo- or hyperthyroidism was not different according to the pattern of menstruation. Conclusion Menstruation status and hormone levels can be influenced by tamoxifen use in reproductive age breast cancer patients. Physicians should be attentive to the alteration of pituitary hormone levels in addition to sex steroid hormones in this population.

Sex Steroid Production from Cryopreserved and Reimplanted Ovarian Tissue

Fertility preservation is an emerging discipline that now has a key place in the care of re‐ productive-aged women with cancer. Because of improvement in diagnostic and therapeu‐ tic strategies, an increasingly larger number of women are surviving with cancer. In the US, more than 11 million are living with cancer and approximately 450,000 cancer survi‐ vors are of reproductive age. In addition, 4-5% of new cancer patients are younger than 35 years [1]. As a result, quality-of-life issues, including those involving fertility preservation, have gained a significant importance in the care of women with cancer.