In Ok Song

Age specific serum anti-Müllerian hormone levels in 1,298 Korean women with regular menstruation

Objective To determine the age specific serum anti-Müllerian hormone (AMH) reference values in Korean women with regular menstruation. Methods Between May, 2010 and January, 2011, the serum AMH levels were evaluated in a total of 1,298 women who have regular menstrual cycles aged between 20 and 50 years. Women were classified into 6 categories by age: 20-31 years, 32-34 years, 35-37 years, 38-40 years, 41-43 years, above 43 years. Measurement of serum AMH was measured by commercial enzyme-linked immunoassay. Results The serum AMH levels correlated negatively with age. The median AMH level of each age group was 4.20 ng/mL, 3.70 ng/mL, 2.60 ng/mL, 1.50 ng/mL, 1.30 ng/mL, and 0.60 ng/mL, respectively. The AMH values in the lower 5th percentile of each age group were 1.19 ng/mL, 0.60 ng/mL, 0.42 ng/mL, 0.27 ng/mL, 0.14 ng/mL, and 0.10 ng/mL, respectively. Conclusion This study determined reference values of serum AMH in Korean women with regular menstruation. These values can be applied to clinical evaluation and treatment of infertile women.

Estimation of chromosomal imbalances in preimplantation embryos from preimplantation genetic diagnosis cycles of reciprocal translocations with or without acrocentric chromosomes

OBJECTIVE To estimate chromosomal imbalances in preimplantation embryos from reciprocal translocation carriers with or without acrocentric chromosomes (Acro-Ch) 13, 14, 15, 21, and 22 in preimplantation genetic diagnosis (PGD) cycles. DESIGN Fluorescence in situ hybridization was applied to PGD cycles for reciprocal translocation carriers. SETTING University-based centers for reproductive medicine. PATIENT(S) Ten and 24 patients of reciprocal translocation with and without Acro-Ch, respectively. INTERVENTION(S) Fluorescence in situ hybridization in biopsied blastomeres. MAIN OUTCOME MEASURE(S) Estimation of meiotic segregation mode in embryos from translocation carriers. RESULT(S) The proportion of alternative segregation for normal or balanced chromosome contents in preimplantation embryos from PGD cycles in reciprocal translocations without Acro-Ch was significantly higher than that with Acro-Ch (26.0% vs. 14.6%). The proportion of interchange trisomy in 3:1 segregation was significantly lower in reciprocal translocations without Acro-Ch than that with Acro-Ch (4.3% vs. 9.5%). CONCLUSION(S) This is the first report that the incidence of alternative segregation producing normal or balanced embryos was relatively low in reciprocal translocations associated with Acro-Ch. Our data may be useful to predict the possibility of normal or balanced embryos and to counsel with reciprocal translocation carriers for PGD-fluorescence in situ hybridization cycles.

Serum anti-Müllerian hormone levels as a predictor of the ovarian response and IVF outcomes

Objective The aim of this study was to investigate whether anti-Mullerian hormone (AMH) levels could be predict ovarian poor/hyper response and IVF cycle outcome. Methods Between May 2010 and January 2011, serum AMH levels were evaluated with retrospective analysis. Three hundred seventy infertile women undergoing 461 IVF cycles between the ages of 20 and 42 were studied. We defined the poor response as the number of oocytes retrieved was equal or less than 3, and the hyper response as more than 25 oocytes retrieved. Serum AMH was measured by commercial enzyme-linked immunoassay. Results The number of oocytes retrieved was more correlated with the serum AMH level (r=0.781, p<0.01) than serum FSH (r=-0.412, p<0.01). The cut-off value of serum AMH levels for poor response was 1.05 ng/mL (receiver operating characteristic [ROC] curves/area under the curve [AUC], ROCAUC=0.85, sensitivity 74%, specificity 87%). Hyper response cut-off value was 3.55 ng/mL (ROCAUC=0.91, sensitivity 94%, specificity 81%). When the study group was divided according to the serum AMH levels (low: <1.05 ng/mL, middle: 1.05 ng/mL - 3.55 ng/mL, high: >3.55 ng/mL), the groups showed no statistical differences in mature oocyte rates (71.6% vs. 76.5% vs. 74.8%) or fertilization rates (76.9% vs. 76.6% vs. 73.8%), but showed significant differences in clinical pregnancy rates (21.7% vs. 24.1% vs. 40.8%, p=0.017). Conclusion The serum AMH level can be used to predict the number of oocytes retrieved in patients, distinguishing poor and high responders.

Molecular and cytogenetic studies of 101 infertile men with microdeletions of Y chromosome in 1,306 infertile Korean men

ObjectivesTo determine the prevalence of Y chromosome microdeletions in infertile Korean men with abnormal sperm counts and to assess the clinical features and frequency of chromosomal abnormalities in Korean patients with microdeletions.MethodsA total of 1,306 infertile men were screened for Y chromosome microdeletions, and 101 of them had microdeletions. These 101 men were then retrospectively studied for cytogenetic evaluation, testicular biopsy and outcomes of IVF and ICSI.ResultsThe overall prevalence of Y chromosome microdeletions in infertile men was 7.7 % (101/1,306). Most microdeletions were in the AZFc region (87.1 %), including deletions of AZFbc (24.7 %) and AZFabc (8.9 %). All patients with AZFa, AZFbc and AZFabc deletions had azoospermia, whereas patients with an AZFc deletion usually had low levels of sperm in the ejaculate or in the testis tissues. Chromosomal studies were performed in 99 men with microdeletions, 36 (36.4 %) of whom had chromosomal abnormalities. Among the infertile men with Y chromosome microdeletions in this study, the incidence of chromosomal abnormality was 48.6 % in the azoospermic group and 3.7 % in the oligozoospermic group. Among the 69 patients with microdeletions and available histological results, 100.0 % of the azoospermic group and 85.7 % of the oligozoospermic group had histological abnormalities. The frequency of both chromosomal abnormalities and histological abnormalities was higher in the azoospermic group compared to the oligozoospermic group. Thirty-four ICSI cycles with either testicular (n = 14) or ejaculated spermatozoa (n = 20) were performed in 23 couples with men with AZFc microdeletion. Thirteen clinical pregnancies (39.4 %) were obtained, leading to the birth of 13 babies.ConclusionsThe study results revealed a close relationship between microdeletions and spermatogenesis, although IVF outcome was not significantly affected by the presence of the AZFc microdeletion. Nevertheless, Y chromosome microdeletions have the potential risk of being transmitted from infertile fathers to their offspring by ICSI. Therefore, before using ICSI in infertile patients with severe spermatogenic defects, careful evaluations of chromosomal abnormalities and Y chromosome microdeletions screening should be performed and genetic counseling should be provided before IVF-ET.

Comparison of assisted reproductive technology outcomes in infertile women with polycystic ovary syndrome: In vitro maturation, GnRH agonist, and GnRH antagonist cycles

Objective We compared the assisted reproductive technology (ART) outcomes among infertile women with polycystic ovary syndrome (PCOS) treated with IVM, conventional IVF, GnRH agonist, and GnRH antagonist cycles. Methods The prospective study included a total of 67 cycles in 61 infertile women with PCOS. The women with PCOS were randomized into three IVF protocols: IVM/IVF with FSH and hCG priming with immature oocyte retrieval 38 hours later (group A, 14 cycles), GnRH agonist long protocol (group B, 14 cycles), and GnRH antagonist multi-dose flexible protocol (group C, 39 cycles). IVF outcomes, such as clinical pregnancy rate (CPR), implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR), were compared among the three groups. Results Age, BMI, and basal FSH and LH levels did not differ among the three groups. The number of retrieved oocytes and 2 pronucleus embryos was significantly lower in group A compared with groups B and C. The CPR, IR, MR, and LBR per embryo transfer showed no differences among the three groups. There was no incidence of ovarian hyperstimulation syndrome in group A. Conclusion The IR, MR, and LBR in the IVM cycles were comparable to those of the GnRH agonist and GnRH antagonist cycles. The IVM protocol, FSH and hCG priming with oocyte retrieval 38 hours later, is an effective ART option that is comparable with conventional IVF for infertile women with PCOS.

Clinical outcomes of preimplantation genetic diagnosis (PGD) and analysis of meiotic segregation modes in reciprocal translocation carriers

Balanced reciprocal translocation is the most common chromosome rearrangement, with an incidence of 1 out of 625 newborns. In reciprocal translocation carriers, genetically unbalanced gametes can be produced through three principal modes of segregation: adjacent‐1, adjacent‐2 and 3:1. In this study, we reviewed 133 cycles of preimplantation genetic diagnosis (PGD) for 65 couples with reciprocal translocation and analyzed pregnancy outcomes and the meiotic segregation mode of gametes of the translocation carriers using fluorescent in situ hybridization (FISH). We found that 285 of 1,508 embryos (18.9%) were normal or balanced. Thirty‐three clinical pregnancies, including eight spontaneous abortions (21.6% per couple), were established. According to the meiotic segregation analysis, the frequencies of 3:1 and 4:0 segregation modes were significantly higher (P < 0.05) in female carriers, and the frequencies of adjacent‐1 and chaotic segregation modes were significantly higher (P < 0.05) in male carriers. Our results indicate that meiotic segregation might be affected by the carriers sex but not by the carriers age or breakpoints.

Predictive value of sperm motility characteristics assessed by computer-assisted sperm analysis in intrauterine insemination with superovulation in couples with unexplained infertility.

Objective To determine whether characteristics of sperm motility obtained by computer-assisted sperm analysis (CASA) could predict pregnancy after intrauterine insemination (IUI) in couples with unexplained infertility. Methods Three hundred eighty-three cycles of intrauterine insemination with superovulation were retrospectively analyzed. Semen analysis was performed with CASA before and after swim-up and the parameters were compared between pregnant and non-pregnant women. Results The pregnancy rate per cycle was 14.1%. Pregnant and non-pregnant women were comparable in terms of age, infertility duration, the number of dominant follicles. While sperm concentration, motility, and parameters such as average path velocity (VAP) and percentage rapid (RAPID) before semen preparation were significantly different between the pregnancy and non-pregnancy groups, there were no differences in sperm parameters when comparing the two groups after preparation. Using a receiver operating characteristic curve to measure sensitivity and specificity, the optimal threshold value for the predictors of pregnancy was revealed to be a concentration of ≥111×106/mL, a motility of ≥51.4%, and RAPID ≥30.1% before preparation for IUI. Conclusion Sperm parameters including concentration, motility, and RAPID before sperm preparation could have predictive value for pregnancy outcome after intrauterine insemination with superovulation in couples with unexplained infertility, and would be helpful when counseling patients before they make the decision to proceed with IVF/ICSI-ET.

Efficacy of testicular sperm chromatin condensation assay using aniline blue-eosin staining in the IVF-ET cycle

Objective This study was performed to evaluate testicular sperm chromatin condensation using aniline blue-eosin (AB-E) staining and its effects on IVF-ET. Methods Chromatin condensation was analyzed using AB-E staining in 27 cases of testicular sperm extraction. There were 19 cases of obstructive azoospermia (OA) and 8 cases of non-obstructive azoospermia (NOA) in IVF-ET. Mature sperm heads were stained red-pink whereas immature sperm heads were stained dark blue. The percentage of sperm chromatin condensation was calculated from the ratio of the number of red-pink sperm to the total number of sperm analyzed. Results The overall percentages of chromatin condensation in OA and NOA were 31.1±11.2% and 26.3±14.4%, respectively. The fertilization rate was significant higher in OA than NOA (p<0.05); however, the rates of good embryos and clinical pregnancy did not show statistical differences. In OA and NOA, statistical differences were not observed in the rate of chromatin condensation, fertilization, good embryos, and clinical pregnancy between the pregnant group and non-pregnant group. Conclusion Chromatin condensation is less stable than OA and showed a low fertilization rate in NOA. While there were no significant differences in chromatin condensation results between NOA and OA, we propose that a pattern of decreased chromatin condensation in NOA is one of the factors of low fertilization results requiring further study.

Poor sperm quality affects clinical outcomes of intracytoplasmic sperm injection in fresh and subsequent frozen-thawed cycles : potential paternal effects on pregnancy outcomes

OBJECTIVE To evaluate objectively whether poor sperm quality affects sequential events from fertilization to delivery in fresh intracytoplasmic sperm injection (ICSI) and subsequent frozen-thawed embryo transfer (ET) cycles. DESIGN Retrospective study. SETTING University-based centers for reproductive medicine. PATIENT(S) For unbiased comparison, 206 cycles were chosen from 1,999 cycles of patients who underwent ICSI-ET and/or subsequent frozen-thawed ET. Cycles met the following criteria: day 3 ET; female age, <40 y; number of retrieved oocytes, >or=5; no split insemination; and no female factors but tubal factor. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The rates of fertilization, embryo implantation, clinical pregnancy, and delivery and sequential embryonic score (SES) were compared between normal-spermatogenesis patients (NSPs) and defective-spermatogenesis patients (DSPs). RESULT(S) Although sum SES, mean SES, and top SES of transferred embryos on day 3 were similar between NSPs and DSPs, the rates of implantation, clinical pregnancy, and delivery of NSPs were significantly higher than those of DSPs. Furthermore, subsequent ET cycles with frozen-thawed embryos in NSPs and DSPs who failed to achieve pregnancy in their fresh cycles showed that rates of implantation and clinical pregnancy also were significantly lower in DSPs. CONCLUSION(S) Quality of sperm may influence embryo implantation and subsequent pregnancy outcomes without impairment of embryo quality.

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/m2 (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/m2) 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.