Investigation of Patient-Centric 3D-Printed Orodispersible Films Containing Amorphous Aripiprazole.

The objective of this study was to design and evaluate an orodispersible film (ODF) composed of aripiprazole (ARP), prepared using a conventional solvent casting technique, and to fuse a three-dimensional (3D) printing technique with a hot-melt extrusion (HME) filament. Klucel® LF (hydroxypropyl cellulose, HPC) and PE-05JPS® (polyvinyl alcohol, PVA) were used as backbone polymers for 3D printing and solvent casting. HPC-, PVA-, and ARP-loaded filaments were applied for 3D printing using HME. The physicochemical and mechanical properties of the 3D printing filaments and films were optimized based on the composition of the polymers and the processing parameters. The crystalline states of drug and drug-loaded formulations were investigated using differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). The dissolution and disintegration of the 3D-printed films were faster than those of solvent-cast films. HPC-3D printed film was fully disintegrated within 45 ± 3.5 s. The dissolution rate of HPC films reached 80% within 30 min at pH 1.2 and pH 4.0 USP buffer. There was a difference in the dissolution rate of about 5 to 10% compared to PVA films at the same sampling time. The root mean square of the roughness (Rq) values of each sample were evaluated using atomic force microscopy. The higher the Rq value, the rougher the surface, and the larger the surface area, the more salivary fluid penetrated the film, resulting in faster drug release and disintegration. Specifically, The HPC 3D-printed film showed the highest Rq value (102.868 nm) and average surface roughness (85.007 nm). The puncture strength of 3D-printed films had desirable strength with HPC (0.65 ± 0.27 N/mm2) and PVA (0.93 ± 0.15 N/mm2) to prevent deformation compared to those of marketed film products (over 0.34 N/mm2). In conclusion, combining polymer selection and 3D printing technology could innovatively design ODFs composed of ARP to solve the unmet medical needs of psychiatric patients.

Mitophagy links oxidative stress conditions and neurodegenerative diseases.

Mitophagy is activated by a number of stimuli, including hypoxia, energy stress, and increased oxidative phosphorylation activity. Mitophagy is associated with oxidative stress conditions and central neurodegenerative diseases. Proper regulation of mitophagy is crucial for maintaining homeostasis; conversely, inadequate removal of mitochondria through mitophagy leads to the generation of oxidative species, including reactive oxygen species and reactive nitrogen species, resulting in various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These diseases are most prevalent in older adults whose bodies fail to maintain proper mitophagic functions to combat oxidative species. As mitophagy is essential for normal body function, by targeting mitophagic pathways we can improve these disease conditions. The search for effective remedies to treat these disease conditions is an ongoing process, which is why more studies are needed. Additionally, more relevant studies could help establish therapeutic conditions, which are currently in high demand. In this review, we discuss how mitophagy plays a significant role in homeostasis and how its dysregulation causes neurodegeneration. We also discuss how combating oxidative species and targeting mitophagy can help treat these neurodegenerative diseases.

The likelihood of achieving pregnancy through timed coitus in young infertile women with decreased ovarian reserve.

OBJECTIVE: To evaluate the pregnancy rate and time to pregnancy after timed coitus with or without superovulation in infertile young women younger than 35 years old with low serum anti-Müllerian hormone (AMH) levels (<25th percentile). METHODS: A total of 202 patients younger than 35 years old were recruited retrospectively between 2010 and 2012. Ninety-eight women had normal serum AMH levels (25-75th percentile), 75 women had low serum AMH levels (5th≤&<25th percentile) and 29 women had very low serum AMH levels (<5th percentile), according to reference values for their age group. RESULTS: The clinical pregnancy rate was positively associated with AMH levels, but this trend did not reach statistical significance (43.9% vs. 41.3% vs. 27.6% in the normal, low, and very low AMH groups, respectively). The time to pregnancy was longer in the very low AMH group than in the normal AMH group (13.1±10.9 months vs. 6.9±6.1 months, p=0.030). The cumulative live birth rate over 18 months was lower in the very low AMH group than in the normal AMH group, with marginal significance (20.0% vs. 55.9%, p=0.051). The duration of infertility was negatively correlated with achieving pregnancy (odds ratio, 0.953; 95% confidence interval, 0.914-0.994; p=0.026). CONCLUSION: Conservative management, such as timed coitus with or without superovulation, should be considered in young patients who have low ovarian reserve without any infertility factors. However, for women with a long duration of infertility or very low serum AMH levels, active infertility treatment should be considered.

Predictors of live birth and pregnancy success after in vitro fertilization in infertile women aged 40 and over.

OBJECTIVE: The aim of this study was to evaluate pregnancy outcomes and the live birth rate at 1-year age increments in women aged ≥40 years undergoing fresh non-donor in vitro fertilization (IVF) and embryo transfer (ET), and to identify predictors of success in these patients. METHODS: This retrospective study was performed among women ≥40 years of age between 2004 and 2011. Of the 2,362 cycles that were conducted, ET was performed in 1,532 (73.1%). RESULTS: The clinical pregnancy rate and live birth rate in women ≥40 years significantly decreased with each year of increased age (p<0.001). Maternal age (odds ratio [OR], 0.644; 95% confidence interval [CI], 0.540-0.769; p<0.001), basal follicle-stimulating hormone (FSH) levels (OR, 0.950; 95% CI, 0.903-0.999; p=0.047), the number of high-quality embryos (OR, 1.258; 95% CI, 1.005 -1.575; p=0.045), and the number of transferred embryos (OR, 1.291; 95% CI, 1.064 -1.566; p=0.009) were significant predictors of live birth. A statistically significant increase in live birth rates was seen when ≥3 embryos were transferred in patients 40 to 41 years of age, whereas poor pregnancy outcomes were seen in patients ≥43 years of age, regardless of the number of transferred embryos. Moreover, the cumulative live birth rate increased in patients 40 to 42 years of age with repeated IVF cycles, but the follicle-stimulating hormone in those ≥43 years of age rarely showed an increase. CONCLUSION: IVF-ET has acceptable outcomes in those <43 years of age when a patient's own oocytes are used. Maternal age, basal FSH levels, and the number of high-quality embryos and transferred embryos are useful predictors of live birth.

Anatomical distributional defects in mutant genes associated with dominant intermediate Charcot-Marie-Tooth disease type C in an adenovirus-mediated mouse model.

Dominant intermediate Charcot-Marie-Tooth disease type C (DI-CMTC) is a dominantly inherited neuropathy that has been classified primarily based on motor conduction velocity tests but is now known to involve axonal and demyelination features. DI-CMTC is linked to tyrosyl-tRNA synthetase (YARS)-associated neuropathies, which are caused by E196K and G41R missense mutations and a single de novo deletion (153-156delVKQV). It is well-established that these YARS mutations induce neuronal dysfunction, morphological symptoms involving axonal degeneration, and impaired motor performance. The present study is the first to describe a novel mouse model of YARS-mutation-induced neuropathy involving a neuron-specific promoter with a deleted mitochondrial targeting sequence that inhibits the expression of YARS protein in the mitochondria. An adenovirus vector system and in vivo techniques were utilized to express YARS fusion proteins with a Flag-tag in the spinal cord, peripheral axons, and dorsal root ganglia. Following transfection of YARS-expressing viruses, the distributions of wild-type (WT) YARS and E196K mutant proteins were compared in all expressed regions; G41R was not expressed. The proportion of Flag/green fluorescent protein (GFP) double-positive signaling in the E196K mutant-type mice did not significantly differ from that of WT mice in dorsal root ganglion neurons. All adenovirus genes, and even the empty vector without the YARS gene, exhibited GFP-positive signaling in the ventral horn of the spinal cord because GFP in an adenovirus vector is driven by a cytomegalovirus promoter. The present study demonstrated that anatomical differences in tissue can lead to dissimilar expressions of YARS genes. Thus, use of this novel animal model will provide data regarding distributional defects between mutant and WT genes in neurons, the DI-CMTC phenotype, and potential treatment approaches for this disease.

Role of Gasotransmitters in Oxidative Stresses, Neuroinflammation, and Neuronal Repair.

To date, three main gasotransmitters, that is, hydrogen sulfide (H2S), carbon monoxide (CO), and nitric oxide (NO), have been discovered to play major bodily physiological roles. These gasotransmitters have multiple functional roles in the body including physiologic and pathologic functions with respect to the cellular or tissue quantities of these gases. Gasotransmitters were originally known to have only detrimental and noxious effects in the body but that notion has much changed with years; vast studies demonstrated that these gasotransmitters are precisely involved in the normal physiological functioning of the body. From neuromodulation, oxidative stress subjugation, and cardiovascular tone regulation to immunomodulation, these gases perform critical roles, which, should they deviate from the norm, can trigger the genesis of a number of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The purpose of this review is to discuss at great length physical and chemical properties and physiological actions of H2S, NO, and CO as well as shedding light on recently researched molecular targets. We particularly put emphasis on the roles in neuronal inflammation and neurodegeneration and neuronal repair.

Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment.

OBJECTIVE: To determine the preferred regimen for women with adenomyosis undergoing in vitro fertilization (IVF), we compared the IVF outcomes of fresh embryo transfer (ET) cycles with or without gonadotropin-releasing hormone (GnRH) agonist pretreatment and of frozen-thawed embryo transfer (FET) cycles following GnRH agonist treatment. METHODS: This retrospective study included 241 IVF cycles of women with adenomyosis from January 2006 to January 2012. Fresh ET cycles without (147 cycles, group A) or with (105 cycles, group B) GnRH agonist pretreatment, and FET cycles following GnRH agonist treatment (43 cycles, group C) were compared. Adenomyosis was identified by using transvaginal ultrasound at the initial workup and classified into focal and diffuse types. The IVF outcomes were also subanalyzed according to the adenomyotic region. RESULTS: GnRH agonist pretreatment increased the stimulation duration (11.5±2.1 days vs. 9.9±2.0 days) and total dose of gonadotropin (3,421±1,141 IU vs. 2,588±1,192 IU), which resulted in a significantly higher number of retrieved oocytes (10.0±8.2 vs. 7.9±6.8, p=0.013) in group B than in group A. Controlled ovarian stimulation for freezing resulted in a significantly higher number of retrieved oocytes (14.3±9.2 vs. 10.0±8.2, p=0.022) with a lower dose of gonadotropin (2,974±1,112 IU vs. 3,421±1,141 IU, p=0.037) in group C than in group B. The clinical pregnancy rate in group C (39.5%) tended to be higher than those in groups B (30.5%) and A (25.2%) but without a significant difference. CONCLUSION: FET following GnRH agonist pretreatment tended to increase the pregnancy rate in patients with adenomyosis. Further large-scale prospective studies are required to confirm this result.

Reproductive outcomes of retransferring retained embryos in blastocyst transfer cycles.

OBJECTIVE: To determine the incidence of embryo retention (ER) in the transfer catheter following embryo transfer (ET) in blastocyst transfer and investigate whether retransferring retained embryos has an impact on reproductive outcomes in patients undergoing in vitro fertilization-ET. METHODS: We retrospectively analyzed the records of 1,131 blastocyst transfers, which comprised 223 single blastocyst transfer (SBT) and 908 double blastocyst transfer (DBT) cycles. Each SBT and DBT group was classified depending on whether ET was performed without retained embryos in the catheter during the first attempt (without-ER group) or whether any retained embryos were found following ET (ER group) for the purpose of comparing reproductive outcomes in a homogenous population. RESULTS: The overall incidence of finding retained embryos was 2.8% (32/1,131). There were no retained embryos in SBT cycles. In DBT cycles, implantation rates (30.0% vs. 26.6%), positive ß-hCG rates (57.2% vs. 56.2%), clinical pregnancy rates (45.3% vs. 46.9%), and live birth rates (38.9% vs. 43.8%) were not significantly different between the without-ER and ER groups. There were no significant differences in the mean birth weight (g) 2,928.4±631.8 vs. 2,948.7±497.8 and the mean gestational age at birth (269.3±17.2 days vs. 264.2±25.7 days). A total of nine cases of congenital birth defects were found in this study population. Eight were observed in the without-ER group and one in the ER group. CONCLUSION: Our results suggest that retransfer of retained embryos does not have any adverse impact on reproductive outcomes in blastocyst transfer cycles. Furthermore, our results support finding that SBT might be advantageous for decreasing the incidence of retained embryos in catheters.

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.

A high response to controlled ovarian stimulation induces premature luteinization with a negative impact on pregnancy outcomes in a gonadotropin-releasing hormone antagonist cycle.

OBJECTIVE: The goal of this study was to investigate the relationship between serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration and the pregnancy rate among women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) using a flexible antagonist protocol. METHODS: This prospective study included 200 IVF and ICSI-ET cycles in which a flexible antagonist protocol was used. The patients were divided into five distinct groups according to their serum P4 levels at the time of hCG administration (0.80, 0.85, 0.90, 0.95, and 1.00 ng/mL). The clinical pregnancy rate (CPR) was calculated for each P4 interval. Statistically significant differences were observed at a serum P4 level of 0.9 ng/mL. These data suggest that a serum P4 concentration of 0.9 ng/mL may represent the optimal threshold level for defining premature luteinization (PL) based on the presence of a significant negative impact on the CPR. RESULTS: The CPR for each round of ET was significantly lower in the PL group defined using this threshold (25.8% vs. 41.8%; p=0.019), and the number of oocytes retrieved was significantly higher than in the non-PL group (17.3±7.2 vs. 11.0±7.2; p=0.001). Elevated serum P4 levels on the day of hCG administration were associated with a reduced CPR, despite the retrieval of many oocytes. CONCLUSION: Measuring serum P4 values at the time of hCG administration is necessary in order to determine the optimal strategy for embryo transfer.

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 effectiveness of earlier oocyte retrieval in the case of a premature luteinizing hormone surge on hCG day in in vitro fertilization-embryo transfer cycles.

OBJECTIVE: To evaluate the efficacy of earlier oocyte retrieval in IVF patients with a premature LH surge on hCG day. METHODS: One hundred forty IVF patients (164 cycles) with premature LH surge on hCG day were included, retrospectively. We divided them into 2 study groups: LH surge with timed ovum pick-up (OPU) 36 hours after hCG injection (group B, 129 premature cycles), and LH surge with earlier OPU within 36 hours after hCG injection (group C, 35 cycles). Control groups were tubal factor infertility without premature LH surge (group A, 143 cycles). RESULTS: The mean age (year) was statistically higher in group C than in groups A or B (38.2±5.4 vs. 36.2±4.2 vs. 36.8±4.9, respectively; p=0.012). The serum LH levels (mIU/mL) on hCG day were significantly higher in group B and C than in group A (22.7±14.9 vs. 30.3±15.9 vs. 3.2±2.9, respectively; p>0.001). Among groups A, B, and C, 4.9%, 31.7%, and 51.4% of the cycles, respectively, had no oocytes, and the overall rates of cycle cancellation (OPU cancellation, no oocyte, or no embryos transferrable) were 15.4%, 65.9%, and 74.3%, respectively. The fertilization rate (%) was significantly higher in group B than in group C (73.2±38.9 vs. 47.8±42.9, p=0.024). The clinical pregnancy rate was significantly higher in group C than in groups A and B (44.4% vs. 27.3% vs. 9.1%, respectively, p=0.021). However, the miscarriage rate was also higher in group C than in group B (22% vs. 0%, respectively, p=0.026). CONCLUSION: Earlier OPU may not be effective in reducing the risk of cycle cancellation in patients with premature LH surge on hCG day. A larger scale study will be required to reveal the effectiveness of earlier ovum retrieval with premature LH surge.

Blastocyst transfer in frozen-thawed cycles.

OBJECTIVE: It is well known that fresh blastocyst transfer results in better pregnancy outcomes with a smaller number of transferred embryos compared with cleavage stage embryo transfer. However, in terms of frozen-thawed blastocyst transfer, only a few studies are available. We aimed to evaluate clinical outcomes of frozen-thawed embryo transfer (FET) with blastocysts. METHODS: Retrospective analysis of FET cycles with blastocysts (B-FET) between Jan 2007 and June 2009 was performed. Age-matched FET cycles with cleavage stage embryos (C-FET) during the same period were collected as controls. A total of 58 B-FET cycles were compared with 172 C-FET cycles and also compared with those of post-thaw extended culture blastocysts from frozen pronuclear stage embryos (22 cycles). RESULTS: There was no difference in the patient characteristics of each group. The embryos' survival rates after thawing were comparable (>90%) and there was no difference in the implantation rate or clinical and ongoing pregnancy rate among the three groups. CONCLUSION: In FET, blastocyst transfers may not present better pregnancy outcomes than cleavage stage embryo transfers. A further large-scale prospective study is needed.

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

OBJECTIVES: To 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: The 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.

Does blastomere biopsy in preimplantation genetic diagnosis affect early serum ß-hCG levels?

OBJECTIVE: To determine whether the serum ß-human chorionic gonadotropin (hCG) profile following preimplantation genetic diagnosis (PGD) is lower than that of intracytoplasmic sperm injection (ICSI) cycles. METHODS: A total of 129 PGD cycles and 1,161 age-matched ICSI cycles, which resulted in pregnancy (serum ß-hCG≥5 mIU/mL) on post-ovulation day (POD) 12 were included. We compared the mean serum ß-hCG levels on POD 12, 14, 21, and 28, doubling time of serum hCG, and created a cut-off value for predicting a singleton pregnancy in each group. RESULTS: The mean serum ß-hCG concentration of the PGD group was significantly lower than that of the control group on POD 12, 14, and 21. The doubling time of serum ß-hCG at each time interval showed no significant difference. The cut-off-value of serum ß-hCG for predicting a single viable pregnancy was 32.5 mIU/mL on POD 12 and 113.5 mIU/mL on POD 14 for the PGD group, which was lower than that for the control group. CONCLUSION: Blastomere biopsy may decrease the ß-hCG-producing activity of the trophoblasts, especially in early pregnancy. Setting a lower cut-off value of serum ß-hCG for predicting pregnancy outcomes in PGD may be needed.

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 ≥111×10(6)/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.

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.

Adverse pregnancy outcomes with assisted reproductive technology in non-obese women with polycystic ovary syndrome: a case-control study.

OBJECTIVE: To investigate adverse pregnancy outcomes in non-obese women with polycystic ovary syndrome (PCOS) compared with obese-PCOS and control groups. METHODS: Women with PCOS who underwent assisted reproductive technology (ART) from August, 2003 to December, 2007, were considered. A total of 336 women with PCOS were included in the study group and 1,003 infertile women who had tubal factor as an indication for ART were collected as controls. They were divided into four groups: a non-obese PCOS group, obese-PCOS group, non-obese tubal factor group, and obese tubal factor group, with obesity defined by a body mass index over 25 kg/m(2), and reviewed focusing on the basal characteristics, ART outcomes, and adverse pregnancy outcomes. RESULTS: There was no difference among the groups' the clinical pregnancy rate or live birth rate. Regarding adverse pregnancy outcomes, the miscarriage rate, multiple pregnancy rate, and prevalence of preterm delivery and pregnancy induced hypertension were not different among the four groups. The incidence of small for gestational age infant was higher in the PCOS groups than the tubal factor groups (p<0.02). On the other hand, the morbidity of gestational diabetes mellitus (GDM) was not high in the non-obese PCOS group but was in the obese groups. And in the obese PCOS group, the newborns were heavier than in the other groups (p<0.02). CONCLUSION: Non-obese PCOS presents many differences compared with obese PCOS, not only in the IVF-parameters but also in the morbidity of adverse pregnancy outcomes, especially in GDM and fetal macrosomia.