• Clinical and Experimental Reproductive Medicine
• /
• v.37 no.1
• /
• pp.49-56
• /
• 2010

Objective: To investigate assisted reproductive technology (ART) outcomes in women with WHO class I anovulation compared with control group. Design: Retrospective case-control study. Methods: Twenty-three infertile women with hypogonadotropic hypogonadism (H-H) who undertook ART procedure from August 2003 to January 2009 were enrolled in this study. A total of 59 cycles (H-H group) were included; Intra-uterine insemination with super-ovulation (SO-IUI, 32 cycles), in vitro fertilization with fresh embryo transfer (IVF-ET, 18 cycles) and subsequent frozenthawed embryo transfer (FET, 9 cycles). Age and BMI matched 146 cycles of infertile women were collected as control group; 64 cycles of unexplained infertile women for SO-IUI and 54 cycles of IVF-ET and 28 cycles of FET with tubal factor. We compared ART and pregnancy outcomes such as clinical pregnancy rate (CPR), clinical abortion rate (CAR), and live birth rate (LBR) between the two groups. Results: There was no difference in the mean age ($32.7{\pm}3.3$ vs. $32.6{\pm}2.7$ yrs) and BMI ($21.0{\pm}3.1$ vs. $20.8{\pm}3.1kg/m^2$) between two groups. Mean levels of basal LH, FSH, and $E_2$ in H-H group were $0.62{\pm}0.35$ mIU/ml, $2.60{\pm}2.30$ mIU/ml and $10.1{\pm}8.2$ pg/ml, respectively. For ovarian stimulation, H-H group needed higher total amount of gonadotropin injected and longer duration for ovarian stimulation (p<0.001). In SO-IUI cycles, there was no significant difference of CPR, CAR, and LBR between the two groups. In IVF-ET treatment, H-H group presented higher mean $E_2$ level on hCG day ($3104.8{\pm}1020.2$ pg/ml vs. $1878.3{\pm}1197.7$ pg/ml, p<0.001) with lower CPR (16.7 vs. 37.0%, p=0.11) and LBR (5.6 vs. 33.3%, p=0.02) and higher CAR (66.7 vs. 10.0%, p=0.02) compared with the control group. However, subsequent FET cycles showed no significant difference of CPR, CAR, and LBR between the two groups. Conclusion: H-H patients need higher dosage of gonadotropin and longer duration for ovarian stimulation compared with the control groups. Significantly poor pregnancy outcomes in IVF-ET cycles of H-H group may be due to detrimental endometrial factors caused by higher $E_2$ level and the absence of previous hormonal exposure on endometrium.

• Clinical and Experimental Reproductive Medicine
• /
• v.26 no.3
• /
• pp.419-432
• /
• 1999

Objective: To establish the evaluation system of the quality of oocytes on the basis of the incidence of cumulus cells apoptosis, to investigate the relationships beween the incidence of cumulus cells and the outcomes of IVF-ET. Method: Thirth-four cycles undergoing controlled ovarian hyperstimulation for IVF-ET with tubal infertility (23 cycles) or unexplained infertility (11 cycles) were included in this study. Cumulus cell masses surrounding mature oocyte and co-culture of embryos with autologous cumulus cells during IVF-ET process. The incidence of apoptosis in cumulus cells was assessed by apoptosis detection kit fluorescein. The effect of co-culture using cumulus cells and the incidence of cumulus cells apoptosis. Results: The results were as follows: 1. The incidence of apoptosis in cumulus cells markedly increased in patients aged 40 or over, while the fertilization rate was greatly decreased in those age group. 2. Apoptosis in cumulus cells was found in both the fertilized oocytes and unfertilized oocytes, but the incidence of apoptosis was higher in unfertilized oocytes. 3. There is no clear correlation between apoptosis in cumulus cells and the number of oocytes retrieved. However, the incidence of apoptosis was increased when the number of oocytes retrieved was 5 and fewer in comparison with $6{\sim}10$. 4. Embryo grade was significantly affected by the incidence of apoptosis in cumulus cells. 5. Pregnancy rate of IVF-ET per cycle was 29.4%, and the pregnant group had the higher fertilization rate and a significantly lower incidence of apoptosis in cumulus cells compared with the nonpregnant group. 6. When cumulus cells were used as helper cells in the co-culture of the embryo, in vitro activity of cumulus cells based on morphological change and proliferation did not influence the quality of embryo, but was closely associated with the implantation rate and pregnancy rate, which was enhanced when morphological changes and proliferation of cumulus cells was more active. 7. This difference in the outcome of IVF-ET according to in vitro activity of cumulus cells used for co-cultue was not associated with the incidence of apoptosis in cumulus cells; but rather had likely relations with the different secretion pattern of protein, which may be an embryo trophic factor by cumulus cells. Conclusion: These results suggest that the incidence of apoptosis in cumulus cells can be used in predicting oocyte qualities and the outcomes of IVF-ET. And the effect of co-culture largely depends on the in vitro activity of cumulus cells as well.

• Clinical and Experimental Reproductive Medicine
• /
• v.37 no.1
• /
• pp.73-81
• /
• 2010

Objective: To examine the efficacy of letrozole in infertile women showing a poor endometrial development at previous ovulation induction cycle by using clomiphene citrate. Methods: Eighteen infertile women were selected who showed a poor endometrial development (endometrial thickness$\leq$6.5 mm) after clomiphene treatment (50~100 mg) as ovulation induction for timed coitus. The mean age of the patients was $30.7{\pm}2.8$ years old and the mean duration of infertility was $33.1{\pm}26.6$ months. The infertility factors were identified as corrected endometriosis (n=1), polycystic ovary syndrome (n=5) and unexplained (n=12). Letrozole was given orally in a dose of 2.5 mg for 5 days starting 3~5 of menstrual cycle. Results: The number of follicles was significantly lower in the letrozole cycle when compared with previous clomiphene cycle ($1.1{\pm}0.3$ vs. $2.2{\pm}1.5$, p=0.011). The endometrial thickness (mm) at the time of triggering or LH surge was significantly greater in the letrozole cycle ($8.4{\pm}1.7$ vs. $5.8{\pm}0.5$, p<0.001). The endometrial pattern 'type C' was significantly higher in the letrozole cycle (94.4% vs. 50%, p=0.036). The pregnancy was achieved in 11.1% of the letrozole cycle. Conclusion: Use of letrozole was associated with more thick and improved endometrium than previous clomiphene cycles in which thin endometrium was identified. Use of letrozole appears to be an effective strategy for second-line treatment in women with inadequate endometrial response to clomiphene.

• Clinical and Experimental Reproductive Medicine
• /
• v.13 no.2
• /
• pp.121-127
• /
• 1986

We have reviewed 59 cases of patients amoung 65 cases who underwent IVF and ET with reasonable indications irom 1984 and the results as follows. 1. Major indications for IVF and ET were tubal factor (40.7%), unexplained infertility (25.4%), endometriosis (15.3%), failed AID and AIH (10.1 %), and sperm abnormality (8.5%). 2. For superovulation of human oocytes, l00mg of clomiphene citrate and 75 IU of HMG used. The monitoring of oocyte maturation was bone by ultrasound examination and serum 17-${\beta}$ estradiol, LH values. The peak $E_2$ value was 956.36${\pm}$702.13 pg/ml. 3. The oocytes were obtained by laparoscopy 24-36 hours after the injection of HCG. 4. The mean numbers of follicles at laparoscopy was 3.06 and the successful rate of laparoscopy was 79.7%. 5. And 165 follicles were aspirated from which 98 oocytes were recovered, 59.4% of all follicles had at least one oocyte aspirated. 21.4% of the eggs were mature, 52.0% were moderate, 26.5%. were immature. 6. 67.3% of oocytes were cleaved and were transferred at 4-6 cell stages. 7. Four pregnancies including one chemical pregnancy and one spontaneous abortion were established by ${\beta}$-subunit, u-hCG and ultrasound examinations.

• Clinical and Experimental Reproductive Medicine
• /
• v.44 no.3
• /
• pp.141-145
• /
• 2017

Objective: Delaying embryo transfer (ET) enables us to select among the embryos available for transfer and is associated with positive effects on implantation and pregnancy outcomes. However, the optimal day for ET of human cleavage-stage embryos remains controversial. Methods: A retrospective study of 3,124 in vitro fertilization/intracytoplasmic sperm injection cycles (2,440 patients) was conducted. We compared the effects of day 2 and 3 ET on rates of implantation and pregnancy outcomes between young maternal age (YMA; < 38 years old, n = 2,295) and old maternal age (OMA; ${\geq}38years\;old$, n = 829) patient groups. Results: The YMA and OMA groups did not differ in terms of patient characteristics except for the proportion of unexplained factor infertility, which was significantly greater in the OMA group, and the proportion of arrested embryos, which was significantly greater in the YMA group. However, the biochemical pregnancy, clinical pregnancy, ongoing pregnancy, abortion, and implantation rates per cycle were not significantly different between day 2 and 3 ET in the YMA group or the OMA group. Conclusion: We suggest that offering patients the opportunity to decide which day would be suitable for ET could be part of a patient-friendly protocol that takes into consideration an infertile woman's circumstances and work schedule by allowing ET to be performed on day 2 instead of the traditional transfer on day 3.

• Clinical and Experimental Reproductive Medicine
• /
• v.48 no.4
• /
• pp.368-373
• /
• 2021

Objective: In this study we aimed to assess anorexigenic peptide levels in patients with or without polycystic ovary syndrome (PCOS) and their effects on assisted reproductive treatment (ART) outcomes. Methods: A prospective case-control study was conducted in a tertiary care university-based ART clinic. Eighty-three patients were included in the study. The PCOS group included 41 patients, and the non-PCOS group included 42 controls. The 2003 Rotterdam criteria were used for PCOS patient selection. The ART indications in the non-PCOS group were tubal factor or unexplained infertility. Venous blood samples were taken on the third day of the menstrual cycle to determine the serum anorexigenic peptide levels. The enzyme-linked immunosorbent assay method was used for laboratory analyses. Results: In the PCOS group, serum obestatin levels were significantly lower than in the control group, but serum anorexigenic peptide levels were similar in PCOS patients with or without clinical pregnancy. Ovarian hyperstimulation syndrome (OHSS) was diagnosed only in PCOS patients, and the obestatin levels of OHSS patients were significantly lower than those of other PCOS patients. Conclusion: Baseline anorexigenic peptide levels did not affect the clinical pregnancy rate in ART cycles. Obestatin may play a role in the pathophysiology of OHSS. This possibility should be confirmed in further research.

• Clinical and Experimental Reproductive Medicine
• /
• v.48 no.2
• /
• pp.163-173
• /
• 2021

Objective: This study aimed to characterize a validated model for predicting oocyte retrieval in controlled ovarian stimulation (COS) and to construct model-based nomograms for assistance in clinical decision-making regarding the gonadotropin protocol and dose. Methods: This observational, retrospective, cohort study included 636 women with primary unexplained infertility and a normal menstrual cycle who were attempting assisted reproductive therapy for the first time. The enrolled women were split into an index group (n=497) for model building and a validation group (n=139). The primary outcome was absolute oocyte count. The dose-response relationship was tested using modified Poisson, negative binomial, hybrid Poisson-E_max, and linear models. The validation group was similarly analyzed, and its results were compared to that of the index group. Results: The Poisson model with the log-link function demonstrated superior predictive performance and precision (Akaike information criterion, 2,704; λ=8.27; relative standard error (λ)=2.02%). The covariate analysis included women's age (p<0.001), antral follicle count (p<0.001), basal follicle-stimulating hormone level (p<0.001), gonadotropin dose (p=0.042), and protocol type (p=0.002 and p<0.001 for short and antagonist protocols, respectively). The estimates from 500 bootstrap samples were close to those of the original model. The validation group showed model assessment metrics comparable to the index model. Based on the fitted model, a static nomogram was built to improve visualization. In addition, a dynamic electronic tool was created for convenience of use. Conclusion: Based on our validated model, nomograms were constructed to help clinicians individualize the stimulation protocol and gonadotropin doses in COS cycles.

• Clinical and Experimental Reproductive Medicine
• /
• v.50 no.1
• /
• pp.44-52
• /
• 2023

Objective: The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro. Methods: Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array. Results: The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1β, IL-6, IL-12, interferon α (IFN-α), IFN-β, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway. Conclusion: The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.