Identification of Single Nucleotide Polymorphisms as Biomarkers for Recurrent Pregnancy Loss in Korean Women.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are reportedly associated with repeated abortion. Thus, genetic analysis based on race is the key to developing accurate diagnostic tests. This study analyzed the genetic polymorphisms of recurrent pregnancy loss (RPL) patients among Korean women compared to the controls. METHODS: In 53 women of RPL group and 50 controls, the genetic analysis was performed. The genotype distribution and allele frequency were analyzed statistically for the difference between the two groups. The association between each SNP marker and RPL risk was analyzed. RESULTS: The genotypes of LEPR, endothelial nitric oxide synthase (eNOS), KDR, miR-27a, miR-449b, and tumor necrosis factor-alpha (TNF-α) were analyzed using odds ratio (OR) with 95% confidence intervals (CIs). Only the AG genotype of miR-449b (A>G) polymorphism showed significant association with the risk of RPL when compared to the AA genotype (OR, 2.39). The combination of GG/AG+GG/CA+AA genotypes for eNOS/miR-449b/TNF-α was associated with 7.36-fold higher risk of RPL (OR, 7.36). The GG/AG+GG combination for eNOS/miR-449b showed 2.43-fold higher risk for RPL (OR, 2.43). The combination of AG+GG/CA+AA genotypes for miR-449b/TNF-α showed a significant association with the risk of RPL (OR, 7.60). From the haplotype-based analysis, the G-G-A haplotype of eNOS/miR-449b/TNF-α and the G-A haplotype of miR-449b/TNF-α were associated with increased risk of RPL (OR, 19.31; OR, 22.08, respectively). CONCLUSION: There is a significant association between the risk of RPL and miR-449b/TNF-α combination, and therefore, genetic analysis for specific combined genotypes can be an important screening method for RPL in Korean women.

Fertility of patients with polycystic ovary syndrome undergoing in vitro fertilization by age.

OBJECTIVE: To evaluate outcomes of in vitro fertilization (IVF) among patients with polycystic ovary syndrome (PCOS) by age. METHODS: In a retrospective study, data were retrieved for patients with PCOS (Rotterdam 2003 criteria) and individuals with tubal factor infertility who underwent IVF at a center in Seoul, South Korea, between January 2003 and August 2012. IVF outcomes were compared by age group (A: 30-32 years; B: 33-35 years; C: 36-38 years; D: 39-41 years). RESULTS: The analysis included 307 women with PCOS and 364 with tubal factor infertility. There was a significant difference between women with PCOS and those with tubal infertility factor in the live birth rate in group B (41.3% vs 28.6%, P=0.038) and in group C (40.4% vs 15.1%, P=0.002). Among women with PCOS, no significant differences in number of retrieved oocytes were observed between the age groups (18.8 ± 9.6, 19.1 ± 10.0, 17.7 ± 7.5, and 17.0 ± 13.8). However, the clinical pregnancy rate was significantly lower in group D than in group C (47.2% vs 18.8%, P=0.042). CONCLUSION: Fertility in patients with PCOS was maintained until age 38 years using IVF. Thereafter, the pregnancy rate decreased, although the number of oocytes retrieved by IVF remained stable.

The Risk Factors and Pregnancy Outcomes of 48 Cases of Heterotopic Pregnancy from a Single Center.

The purpose of this study was to investigate risk factors that are associated with heterotopic pregnancy (HP) following in vitro fertilization (IVF)-embryo transfer (ET) and to demonstrate the outcomes of HP after the surgical treatment of ectopic pregnancies. Forty-eight patients from a single center, who were diagnosed with HP between 1998 and 2012 were included. All of the patients had received infertility treatments, such as Clomid with timed coitus (n = 1, 2.1%), superovulation with intrauterine insemination (n = 7, 14.6%), fresh non-donor IVF-ET (n = 33, 68.8%), and frozen-thawed cycles (n = 7, 14.6%). Eighty-four additional patients were randomly selected as controls from the IVF registry database. HP was diagnosed at 7.5 ± 1.2 weeks (range 5.4-10.3) gestational age. In six cases (12.5%), the diagnosis was made three weeks after the patients underwent treatment for abortion. There were significant differences in the history of ectopic pregnancy (22.5% vs. 3.6%, P = 0.002). There were no significant differences in either group between the rates of first trimester intrauterine fetal loss (15.0% vs. 13.1%) or live birth (80.0% vs. 84.1%) after the surgical treatment for ectopic pregnancy. The risk factors for HP include a history of ectopic pregnancy (OR 7.191 [1.591-32.513], P = 0.010), abortion (OR 3.948 [1.574-9.902], P = 0.003), and ovarian hyperstimulation syndrome (OHSS) (OR 10.773 [2.415-48.060], P = 0.002). In patients undergoing IVF-ET, history of ectopic pregnancy, abortion, and OHSS may be risk factors for HP as compared to the control group of other IVF patients. The surgical treatment of HP does not appear to affect the rates of first trimester fetal loss or live birth.

Early gonadotropin-releasing hormone antagonist start improves follicular synchronization and pregnancy outcome as compared to the conventional antagonist protocol.

OBJECTIVE: To assess whether an early GnRH antagonist start leads to better follicular synchronization and an improved clinical pregnancy rate (CPR). METHODS: A retrospective cohort study. A total of 218 infertile women who underwent IVF between January 2011 and February 2013. The initial cohort (Cohort I) that underwent IVF between January 2011 and March 2012 included a total of 68 attempted IVF cycles. Thirty-four cycles were treated with the conventional GnRH antagonist protocol, and 34 cycles with an early GnRH antagonist start protocol. The second cohort (Cohort II) that underwent IVF between June 2012 and February 2013 included a total of 150 embryo-transfer (ET) cycles. Forty-three cycles were treated with the conventional GnRH antagonist protocol, 34 cycles with the modified early GnRH antagonist start protocol using highly purified human menopause gonadotropin and an addition of GnRH agonist to the luteal phase support, and 73 cycles with the GnRH agonist long protocol. RESULTS: The analysis of Cohort I showed that the number of mature oocytes retrieved was significantly higher in the early GnRH antagonist start cycles than in the conventional antagonist cycles (11.9 vs. 8.2, p=0.04). The analysis of Cohort II revealed higher but non-significant CPR/ET in the modified early GnRH antagonist start cycles (41.2%) than in the conventional antagonist cycles (30.2%), which was comparable to that of the GnRH agonist long protocol cycles (39.7%). CONCLUSION: The modified early antagonist start protocol may improve the mature oocyte yield, possibly via enhanced follicular synchronization, while resulting in superior CPR as compared to the conventional antagonist protocol, which needs to be studied further in prospective randomized controlled trials.

Can high serum anti-Müllerian hormone levels predict the phenotypes of polycystic ovary syndrome (PCOS) and metabolic disturbances in PCOS patients?

OBJECTIVE: To evaluate correlations between serum anti-Müllerian hormone (AMH) levels, phenotypes of polycystic ovary syndrome (PCOS), obesity, and metabolic parameters in patients with PCOS. METHODS: A total of 175 patients with PCOS were diagnosed according to the Rotterdam Consensus were included. Exclusion criteria were age over 40, FSH>25 mIU/mL, and 17a-OHP>1.5 ng/mL. The Phenotypes of PCOS were divided into a severe form (oligo-anovulation, ANOV/hyperandrogenism/polycystic ovary morphology [PCOM]; n=59) and a mild form without HA (ANOV/PCOM, n=105). The serum AMH levels were classified into 3 groups (<5 vs. 5-10 vs. >10 ng/mL). Obesity was defined as body mass index (BMI) ≥25 kg/m(2) (n=34). RESULTS: The mean age was 25.9±5.7 year and mean AMH level was 10.1±5.4 ng/mL. The BMI (kg/m(2)) was higher in group 1 (24.2±6.3) than in group 2 (21.9±4.3, p=0.046) or group 3 (21.6±3.3, p=0.019). There was no difference among the three groups in age, menstrual interval, antral follicle counts, androgens, or other metabolic parameters. The obesity group showed significantly lower AMH (7.7±3.9 ng/mL vs. 10.7±5.6 ng/mL), p=0.004) and low-density lipoprotein levels (93.1±21.2 mg/dL vs. 107.5±39.3 mg/dL, p=0.031), and showed higher total T (0.74±0.59 ng/mL vs. 0.47±0.36 ng/mL, p=0.001), free T (2.01±1.9 vs. 1.04±0.8 pg/mL, p=0.0001), and free androgen index (6.2±7.9 vs. 3.5±3.0, p=0.003). After controlling for age factors and BMI, the serum AMH levles did not show any significant correlations with other hormonal or metabolic parmeters. CONCLUSION: For PCOS patients under the age 40, serum AMH is not negatively correlated with age. High serum AMH levels can not predict the phenotype of PCOS and metabolic disturbances in PCOS patients in the non-obese group. Further study might be needed to define the relation more clearly.

The feasibility of scarless single-port transumbilical total laparoscopic hysterectomy: initial clinical experience.

OBJECTIVE: The purpose of the present study is to demonstrate the feasibility of single-port transumbilical laparoscopic surgery (SPLS) for hysterectomy and elaborate on our experience in order to introduce the single-port approach for gynecologic surgery. METHODS: Between August 2008 and February 2009, 30 patients who initially planned to undergo single-port laparoscopic surgery at Yonsei University Health System in Seoul, Korea were enrolled in this study. The authors used a single-port three-channel system with a wound retractor, surgical gloves, and one 10/11-mm and two 5-mm trocars. All surgical procedures were performed with 30 degrees , 5-mm laparoscope, conventional laparoscopic instruments, and the LigaSure system (Valleylab, Boulder, CO, USA). Patient characteristics and surgical outcomes were prospectively evaluated. A visual analog score (VAS) scale was used to measure postoperative pain. RESULTS: Twenty-nine of 30 patients underwent single-port laparoscopic surgery without conversion to laparotomy or conventional laparoscopic hysterectomy. Median operative time was 100 min (57-155 min), median blood loss was 100 ml (10-400 ml), median postoperative hospital stay was 3 days (2-6 days), and median weight of resected uteri was 167 g (45-482 g). VAS scoring of pain at 6, 24, and 48 h after surgery was 4, 3, and 2, respectively. There were no operative complications. CONCLUSION: SPLS is a feasible approach for hysterectomy in terms of operative time, complication rates, and cosmetic results. However, the possible benefits for patients such as better cosmetic outcomes, reduced pain, and lower complication rates should be evaluated in randomized prospective studies.