[Show abstract][Hide abstract] ABSTRACT: Elevated serum progesterone (P) levels on triggering day have been known to affect the pregnancy rate of in vitro fertilization (IVF). This study aimed to identify the possible factors influencing serum P levels on triggering day in stimulated IVF cycles.
Three hundred and thirty consecutive fresh IVF cycles were included in the study. All cycles were first attempts and were performed in a single infertility center. The indications for IVF were male factor infertility (n=114), ovulatory infertility (n=84), endometriosis (n=61), tubal infertility (n=59), unexplained infertility (n=41), and uterine factor infertility (n=39). A luteal long protocol of a gonadotropin-releasing hormone (GnRH) agonist (n=184) or a GnRH antagonist protocol (n=146) was used for pituitary suppression. Ovarian sensitivity was defined as the serum estradiol level on triggering day per 500 IU of administered gonadotropins (OS[a]) or the retrieved oocyte number per 500 IU of administered gonadotropins (OS[b]).
Univariate analysis revealed that the serum P level on triggering day was associated with the serum estradiol level on triggering day (r=0.379, p<0.001), the number of follicles ≥14 mm (r=0.247, p<0.001), the number of retrieved oocytes (r=0.384, p<0.001), and ovarian sensitivity (OS[a]: r=0.245, p<0.001; OS[b]: r=0.170, p=0.002). The woman's age, body mass index, antral follicle count, and basal serum follicle stimulating hormone and estradiol levels were not associated with serum P level on triggering day. The serum P level on triggering day did not show significant variation depending on the type or cause of infertility, pituitary suppression protocol, or the type of gonadotropins used.
The serum P level on triggering day was closely related to the response to ovarian stimulation.
Clinical and Experimental Reproductive Medicine 06/2015; 42(2):67-71. DOI:10.5653/cerm.2015.42.2.67
[Show abstract][Hide abstract] ABSTRACT: To investigate the effect of antifreeze protein (AFP) supplementation on ovarian vitrification and transplantation.
In this experimental study, we researched a total of 182 ovaries from 4-week-old ICR mice. The equilibration solution included 20% ethylene glycol (EG), and the vitrification solution included 40% EG, 18% Ficoll, and 0.3 M sucrose. Intact ovaries were first suspended in 1 mL of equilibration solution for 10 min, and then mixed with 0.5 mL of vitrification solution for 5 min. Ovaries were randomly assigned to 3 groups and 0, 5, or 20 mg/mL of type III AFP was added into the vitrification solution (control, AFP5, and AFP20 groups, respectively). The vitrified ovaries were evaluated after warming and 2 weeks after autotransplantation. The main outcome measurements are follicular morphology and apoptosis assessed by histology and the TUNEL assay.
A significantly higher intact follicle ratio was shown in the AFP treated groups (control, 28.9%; AFP5, 42.3%; and AFP20, 44.7%). The rate of apoptotic follicles was significantly lower in the AFP treated groups (control, 26.6%; AFP5, 18.7%; and AFP20, 12.6%). After transplantation of the vitrified-warmed ovaries, a significantly higher intact follicle ratio was shown in the AFP20 group. The rate of apoptotic follicles was similar among the groups.
The results of the present study suggest that supplementing AFP in the vitrification solution has beneficial effects on the survival of ovarian tissue during cryopreservation and transplantation.
Yonsei medical journal 05/2015; 56(3):778-84. DOI:10.3349/ymj.2015.56.3.778 · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The study aimed to evaluate the feasibility and reproducibility of measuring phospholipase C zeta (PLCζ) using immunostaining in human sperm and to investigate the relationship between PLCζ immunoreactivity and DNA fragmentation and oxidation in human sperm.
Semen samples were obtained from participants (n=44) and processed by the conventional swim-up method. Sperm concentration, motility, normal form by strict morphology, DNA fragmentation index assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling method and immunofluorescent expression for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and PLCζ were assessed.
When duplicate PLCζ tests were performed on two sperm samples from each of the 44 participants, similar results were obtained (74.1±9.4% vs. 75.4±9.7%). Two measurements of PLCζ were found to be highly correlated with each other (r=0.759, P<0.001). Immunoreactivity of PLCζ was not associated with donor's age, sperm concentration, motility, and the percentage of normal form as well as DNA fragmentation index. However, immunoreactivity of PLCζ showed a significant negative relationship with 8-OHdG immunoreactivity (r=-0.404, P=0.009).
Measurement of PLCζ by immunostaining is feasible and reproducible. Lower expression of PLCζ in human sperm may be associated with higher sperm DNA oxidation status.
[Show abstract][Hide abstract] ABSTRACT: To compare the laboratory outcomes of intracytoplasmic sperm injection (ICSI) and conventional insemination using sibling oocytes in poor prognosis IVF cycles where ICSI is not indicated.
Couples undergoing IVF with following conditions were enrolled: history of more than 3 years of unexplained infertility, history of ≥3 failed intrauterine insemination, leukocytospermia or wide variation in semen analysis, poor oocyte quality, or ≥50% of embryos had poor quality in previous IVF cycle(s). Couples with severe male factor requiring ICSI were excluded. Oocytes were randomly assigned to the conventional insemination (conventional group) or ICSI (ICSI group). Fertilization rate (FR), total fertilization failure, and embryonic development at day 3 and day 5 were assessed.
A total of 309 mature oocytes from 37 IVF cycles (32 couples) were obtained: 161 were assigned to conventional group and 148 to ICSI group. FR was significantly higher in the ICSI group compared to the conventional group (90.5% vs. 72.7%, P<0.001). Total fertilization failure occurred in only one cycle in conventional group. On day 3, the percentage of cleavage stage embryos was higher in ICSI group however the difference was marginally significant (P=0.055). In 11 cycles in which day 5 culture was attempted, the percentage of blastocyst (per cleaved embryo) was significantly higher in the ICSI group than the conventional group (55.9% vs. 25.9%, P=0.029).
Higher FR and more blastocyst could be achieved by ICSI in specific circumstances. Fertilization method can be tailored accordingly to improve IVF outcomes.
[Show abstract][Hide abstract] ABSTRACT: This study attempted to derive an objective and sophisticated definition of poor ovarian response (POR).
A total of 176 consecutive in vitro fertilization (IVF) cycles (137 patients) with conventional ovarian stimulation during 2009 to 2012 were studied by retrospective analysis. Optimal oocyte number (total or mature) was determined by statistics-based (distribution of oocyte number) and prognosis-based approaches (prediction for IVF outcome). Receiver operating characteristics curve analysis was used to show what number of oocytes could predict IVF pregnancy and whether clinical and laboratory variables could predict newly defined POR.
The 25th percentile of the distribution corresponded to total oocytes ≤2 and mature oocyte ≤1. The cut-off values for the prediction of IVF outcomes were total oocytes >5 and mature oocyte >1. Considering the incidence of POR (34.1%), a reasonable definition of POR was decided as total oocytes ≤2 or mature oocyte ≤1. For the prediction of this new definition, the extreme cut-off value (by setting a false positive rate of 5%) of serum anti-Mullerian hormone (AMH) was ≤0.76 ng/mL, which was better than serum follicle stimulating hormone or age. A new simple definition of POR was derived as total oocytes ≤2 or mature oocyte ≤1 in a previous cycle or a serum AMH level of ≤0.76 ng/mL. When this simple criterion was re-applied to our data, the predictive performance was similar to the Bologna criteria.
We here propose a new definition of POR, which is simple and supported by statistical and prognostic analyses.
Yonsei Medical Journal 03/2015; 56(2):482-9. DOI:10.3349/ymj.2015.56.2.482 · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aimed to evaluate the efficacy of random-start controlled ovarian stimulation (COS) in cancer patients for emergency fertility preservation. In this retrospective comparative study, 22 patients diagnosed with cancer and 44 infertile women undergoing conventional in vitro fertilization (IVF) were included. In cancer patients, ovarian stimulation was started on the day of referral, irrespective of their menstrual cycle date. The control group was selected by age matching among women undergoing conventional IVF. COS outcomes were compared between groups. The number of total and mature oocytes retrieved and the oocyte maturity rate were higher in the random-start group than in the conventional-start group. However, duration of ovarian stimulation was longer in the random-start group (11.4 vs. 10.3 days, P = 0.004). The addition of letrozole to lower the estradiol level during COS did not adversely affect total oocytes retrieved. However, oocyte maturity rate was lower in cycles with letrozole than in cycles without letrozole (71.6% vs. 58.2%, P = 0.019). Our study confirms the feasibility and effectiveness of random-start COS in cancer patients.
Journal of Korean Medical Science 03/2015; 30(3):290-5. DOI:10.3346/jkms.2015.30.3.290 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report the various anatomic locations of surgically and pathologically proven endometriosis.
Pathologic reports (n=1,376) of women who underwent surgeries at a single center between April 2005 and March 2013 were retrieved from the electronic medical record system of the hospital. Pathologic reports were included after performing a search by using the key-words "endometrial cyst," "endometriotic cyst," "endometriosis," or "endometrioma." Only reports dealing with female patients were selected, and the pathologic reports of 1,350 women (1,374 surgery cases) were included in the analysis.
The predominant location of endometriosis was the ovaries (96.4%), followed by the soft tissue (2.8%), gastrointestinal tract (0.3%) and urinary tract (0.2%). Laparoscopic surgery was the major surgical technique used for the pelvic endometriosis (89.2%). Adrenal gland endometriosis was found in a 55-year-old woman.
We established the various anatomic locations of surgically and pathologically proven endometriosis in Korean women.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the association between the severity of endometriosis and the preoperative neutrophil-to-lymphocyte ratio (NLR) and serum level of cancer antigen 125 (CA 125).
Data were obtained from the medical records of 419 patients who underwent laparoscopic conservative surgery for ovarian endometrioma between April 2005 and March 2013. Each patient's preoperative complete blood count was recorded and the endometriosis score was assessed.
The endometriosis score was not associated with either the NLR or the serum level of CA 125. The endometriosis score was negatively related to preoperative hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. The only positive association was between NLR and the patients' age. NLR and preoperative serum anti-Müllerian hormone level were found to be negatively related.
The severity of endometriosis was not associated with the serum level of CA 125 or the NLR. The presence of a negative correlation between the severity of endometriosis and red blood cell dynamics needs further investigation.
Clinical and Experimental Reproductive Medicine 12/2014; 41(4):151-7. DOI:10.5653/cerm.2014.41.4.151
[Show abstract][Hide abstract] ABSTRACT: Necrostatin 1 (Nec1) is widely used in disease models to examine the contribution of receptor-interacting protein kinase 1 in cell death. The biological actions of Nec1 are blocking necrotic cell death. The purpose of this study was to investigate whether adding Nec1 into in vitro maturation (IVM) media, followed by vitrification procedures, could enhance the survival and developmental competency of oocytes. Germinal vesicle oocytes were matured in IVM medium containing 2 different doses of Nec1 (0.5 and 1 μmol/L). After IVM, the oocytes were vitrified using a 2-step exposure to equilibrium and vitrification solutions. After warming, the rates of survival, fertilization, embryonic development up to blastocyst in vitro, morphology of spindle and chromosome, membrane integrity, mitochondria integrity, and several gene expressions were evaluated. The survival and developmental competency of oocytes were higher in the 1 μmol/L Nec1-treated group than control. The proportion with intact spindles/chromosomes and stable membranes was similar in all the groups. The mitochondrial integrity of all Nec1-treated groups showed a higher score with strong staining. The 1 μmol/L Nec1 showed significantly increased expressions of Mad2, Gdf9, and Bcl2. The Cirp level had a tendency to be downregulated in the 0.5 µmol/L Nec1 but upregulated in the 1 μmol/L Nec1, compared with the control. The Mtgenome expressions were significantly decreased in both Nec1 groups. The supplementation of 1 μmol/L Nec1 into the IVM medium could be beneficial for the survival and development of immature oocytes after vitrification.
[Show abstract][Hide abstract] ABSTRACT: Objective
To study variations in semen parameters among cancer patients who visited a sperm banking clinic before undergoing cancer treatment.
Retrospective, consecutive study.
Eighty-six patients, diagnosed with various cancers, undergoing multiple semen collections on 5 consecutive days, for fertility preservation, between 2004 and 2013.
Main Outcome Measures
Within- and between-subject coefficients of variation were estimated using a random-effects analysis of variance to assess the consistency of semen parameters (volume, sperm concentration, motility, rapid motility, total motile sperm count, and computer-based sperm parameters), whereas intraclass correlation coefficients (ICCs) were calculated to assess the size of the between-component of variance relative to the total component of variance.
When analyzing semen parameters over a maximum of 5 consecutive days, only the semen volume was significantly reduced in day-1 and -3 samples compared with the first sample. Almost all of the parameters showed high ICC values, suggesting that within-subject fluctuations were small relative to the between-subject variability. The highest ICC values were noted in volume (ICC 0.76; 95% confidence interval [CI] 0.52–0.89), followed by total motile count (ICC 0.71; 95% CI 0.30–0.89); the least consistent measure was wobble (ICC 0.14; 95% CI −0.13, 0.51).
Repeated ejaculates from cancer patients did not show substantial variation in semen quality.
Fertility and Sterility 10/2014; 102(4). DOI:10.1016/j.fertnstert.2014.06.045 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To investigate the incidence of actinomyces-like organisms in routine cervical smears of Korean women and to evaluate its association with the development of pelvic inflammatory disease (PID) in these women.
The results of cervical smears between 2011 and 2012 at a single university hospital were searched. If positive for actinomyces-like organisms, the medical record of the patient was searched and development of PID was followed. If the data were not available in the medical record, the patient was contacted by telephone.
The incidence of actinomyces-like organisms in cervical smears was 0.26% (52/20,390). Forty-two women (80.8%) were intrauterine device (IUD) users: the copper-IUD in 25 women and the levonorgestrel-releasing intrauterine system in 13 women (type unknown in 4 women). The majority (71.4%, 30/42) of the IUD users maintained the IUD. Prophylactic antibiotics were prescribed to 12 women. Two continuous IUD users were later diagnosed with PID, but these cases were not pelvic actinomycosis.
It would be a reasonable option to choose the expectant management for asymptomatic women who incidentally showed actinomyces-like organisms in their cervical smear.
[Show abstract][Hide abstract] ABSTRACT: Purpose
The aim of this work was to evaluate nuclear histone acetylation level and total histone acetyltransferase (HAT) and deacetylase (HDAC) activity in ejaculated sperm and their relevance to conventional sperm parameters.
Materials and Methods
Thirty-three normozoospermic men were included in this study. Semen samples were processed by swim-up and then immunostained by six acetylation antibodies (H3K9ac, H3K14ac, H4K5ac, H4K8ac, H4K12ac, and H4K16ac). Our preliminary study verified the expression of HAT/HDAC1 in mature human sperm. From vitrified-warmed sperm samples, total HAT/HDAC activity was measured by commercially available kits. Nuclear DNA integrity was also measured by TUNEL assay.
The levels of six acetylation marks were not related with conventional sperm parameters including sperm DNA fragmentation index (DFI) as well as HAT/HDAC activity. However, sperm DFI was positively correlated with HAT activity (r=0.038 after adjustment, p<0.02). HAT activity showed a negative relationship with HDAC activity (r=-0.51, p<0.01). Strict morphology was negatively correlated with acetylation enzyme index (=HAT activity/HDAC activity) (r=-0.53, p<0.01).
Our works demonstrated a significant relationship of acetylation-associated enzyme activity and strict morphology or sperm DFI.
Yonsei Medical Journal 09/2014; 55(5):1333-40. DOI:10.3349/ymj.2014.55.5.1333 · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To evaluate the dose effect of recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) or brain-derived neurotrophic factor (BDNF) in culture medium on the development of in vitro fertilized mouse embryos.
Mature oocytes were retrieved from superovulated female BDF1 mice and inseminated by sperm from male BDF1 mice. On day 1, two-cell stage embryos were divided and cultured until day 5 in the embryo maintenance medium supplemented with 0, 1, 2, 5, or 10 ng/mL of rmGM-CSF or supplemented with 0, 5, 10, or 20 ng/mL of BDNF. Blastocyst formation rate and their cell numbers were assessed.
The blastocyst formation rate and the total cell count in blastocyst was similar in all the rmGM-CSF treatment groups when compared with the control. However, the blastocyst formation rate and the total cell count was significantly higher in the group supplemented with 10 ng/mL of BDNF compared with the control (63.9%, 45.8±11.5 vs. 52.3%, 38.0±6.8; P<0.05, respectively).
Supplementation of 10 ng/mL of BDNF enhanced the developmental potential of mouse preimplantation embryos, but supplementation of rmGM-CSF did not.