• Clinical and Experimental Reproductive Medicine
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• v.26 no.1
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• pp.31-41
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• 1999

To evaluate the effectiveness of intrauterine insemination (IUI) in the treatment of infertility, timed-intercourse and intrauterine insemination by husband in stimulated cycles with clomiphene citrate and gonadotropins were compared in a total of 105 cycles. Patients received 100mg of clomiphene citrate daily for 5 days starting on day 3 of the menstrual cycle followed by hMG or FSH. Doses of exogenous gonadotropins were adjusted by the follicular development and concentrations of serum estradiol $(E_2)$. More than 3 follicles reaching >16 mm were present in the ovary, 5,000 IU of hCG was administered intramusculary. Patients received a maximum of three intercourse or IUI cycles for the treatment. Severe male (<$10{\times}10^6$ motile sperm) or age factor (>39 y) patients were excluded in this study. Pregnancy was classified as clinical if a gestational sac or fetal cardiac activity was seen on ultrasound. The overall clinical pregnancy rates were 17.1% per cycle (18/105) and 21.2% per patient (18/85). The pregnancy rates (per cycle) were 17.5% (11/63) in intercourse and 16.7% (7/42) in IUI groups, respectively. IUI had no significant improvement in pregnancy rate compared with timed-intercourse. The multiple pregnancy rates were 11.1% (1 twin and 1 triplet). No patient developed ovarian hyperstimulation. Abortion rate was 28.6% (2/7) in IUI group only. The delivery and ongoing pregnancy rates were 15.2% per cycle (16/105) and 18.8% per patient (16/85). There were no differences in age, duration of infertility, follicle size and level of estradiol $(E_2)$ on the day of hCG injection in pregnant and non-pregnant groups. However, total doses of gonadotropins were higher in pregnant group than in non-pregnant group (p<0.01). Pregnancy rate was not affected by ovulatory status at the time of insemination. These results indicate that well timed-intercourse in stimulated cycles is as effective as IUI for infertile couples.

• Clinical and Experimental Reproductive Medicine
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• v.13 no.2
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• pp.121-127
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• 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
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• v.26 no.3
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• pp.433-440
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• 1999

Objective: To evaluate the effectiveness of CC+FSH or CC+hMG in intrauterine insemination (IUI) cycles for the treatment of infertility. Method: Patients received daily 100 mg of clomiphene citrate (CC) for 5 days followed by hMG or FSH. A single IUI was performed at 36 h after hCG. Clinical pregnancy was classified if a gestational sac or fetal cardiac activity was seen on ultrasound. Results: The overall clinical pregnancy rate was 19.1% per cycle (17/89) and 21.5% per patient (17/79). More clinical pregnancies were recorded in CC+FSH (23.1%, 6/26) than CC+ hMG cycles (17.5%, 11/63), but this difference was not statistically significant. No differences were found in age, duration of infertility, follicle size, levels of estradiol ($E_2$) on the day of hCG injection and total motile sperm counts between pregnant and non-pregnant groups. However, more ampules of gonadotropins were used in pregnant group than non-pregnant group (p<0.05). Conclusion: Combination of CC and hMG may economically be more effective to induce ovulation for IUI compared to CC and FSH.

• Clinical and Experimental Reproductive Medicine
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• v.41 no.1
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• pp.21-28
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• 2014

Objective: To investigate the association of individual follicular fluid (FF) leptin and adiponectin levels with the quality of the corresponding oocyte and embryo. Methods: We prospectively enrolled 67 women who underwent controlled ovarian hyperstimulation with 89 FF samples. FF and the corresponding oocyte was obtained from a single dominant preovulatory follicle at the time of oocyte retrieval. Concentrations of leptin and adiponectin were measured by enzyme-linked immunosorbent assay in an individual follicle. The oocyte quality, fertilization rate, and corresponding embryo development were assessed. Results: The FF level of leptin was significantly associated with body mass index (r=0.334, p<0.01). The FF adiponectin level was significantly higher in the normal fertilization group than the abnormal fertilization group (p=0.009) in the non-obese women. A lower FF leptin level was associated with a trend toward mature oocytes, normal fertilization, and good embryo quality, although these relationships were not statistically significant. The leptin:adiponectin ratio of FF did not differ significantly according to oocyte and embryo quality. The quality of the oocyte and embryo was not associated with the FF leptin level tertile. However, the normal fertilization rate was positively associated with FF adiponectin level tertile. There was a trend towards improved oocytes and normal fertilization rates with the lowest tertile of the FF leptin:adiponectin ratio, but this difference was not statistically significant. Conclusion: Our results suggest that a high FF adiponectin concentration could be a predictor of normal fertilization. However, the FF leptin concentration and leptin:adiponectin ratio is not significantly related to oocyte maturity and corresponding embryo development.

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

• Development and Reproduction
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• v.24 no.4
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• pp.297-306
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• 2020

Repetitive changes in the intracellular calcium concentration ([Ca²⁺]i) triggers egg activation, including cortical granule exocytosis, resumption of second meiosis, block to polyspermy, and initiating embryonic development. [Ca²⁺]i oscillations that continue for several hours, are required for the early events of egg activation and possibly connected to further development to the blastocyst stage. The sources of Ca²⁺ ion elevation during [Ca²⁺]i oscillations are Ca²⁺ release from endoplasmic reticulum through inositol 1,4,5 tri-phosphate receptor and Ca²⁺ ion influx through Ca²⁺ channel on the plasma membrane. Ca²⁺ channels have been characterized into voltage-dependent Ca²⁺ channels (VDCCs), ligand-gated Ca²⁺ channel, and leak-channel. VDCCs expressed on muscle cell or neuron is specified into L, T, N, P, Q, and R type VDCs by their activation threshold or their sensitivity to peptide toxins isolated from cone snails and spiders. The present study was aimed to investigate the localization pattern of N and P/Q type voltage-dependent calcium channels in mouse eggs and the role in fertilization. [Ca²⁺]i oscillation was observed in a Ca²⁺ contained medium with sperm factor or adenophostin A injection but disappeared in Ca²⁺ free medium. Ca²⁺ influx was decreased by Lat A. N-VDCC specific inhibitor, ω-Conotoxin CVIIA induced abnormal [Ca²⁺]i oscillation profiles in SrCl₂ treatment. N or P/Q type VDC were distributed on the plasma membrane in cortical cluster form, not in the cytoplasm. Ca²⁺ influx is essential for [Ca²⁺]i oscillation during mammalian fertilization. This Ca²⁺ influx might be controlled through the N or P/Q type VDCCs. Abnormal VDCCs expression of eggs could be tested in fertilization failure or low fertilization eggs in subfertility women.

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

• Women's Health Nursing
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• v.26 no.4
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• pp.300-317
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• 2020

Purpose: Hysteroscopy can be used both to diagnose and to treat intrauterine pathologies. It is well known that hysteroscopy helps to improve reproductive outcomes by treating intrauterine pathologies. However, it is uncertain whether hysteroscopy is helpful in the absence of intrauterine pathologies. This study aimed to confirm whether hysteroscopy improves the reproductive outcomes of infertile women without intrauterine pathologies. Methods: We conducted a systematic review of 11 studies retrieved from Ovid-MEDLINE, Ovid-Embase, and the Cochrane Library. Two independent investigators extracted the data and used risk-of-bias tools (RoB 2.0 and ROBINS-I) to assess their quality. Results: Diagnostic hysteroscopy prior to in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) was associated with a higher clinical pregnancy rate (CPR) and live birth rate (LBR) than non-hysteroscopy in patients with recurrent implantation failure (RIF) (odds ratio, 1.79 and 1.46; 95% confidence interval, 1.40-2.30 and 1.08-1.97 for CPR and LBR, respectively) while hysteroscopy prior to first IVF was ineffective. The overall meta-analysis of LBR showed statistically significant findings for RIF, but a subgroup analysis showed effects only in prospective cohorts (odds ratio, 1.40 and 1.47; 95% confidence interval, 0.62-3.16 and 1.04-2.07 for randomized controlled trials and prospective cohorts, respectively). Therefore, the LBR should be interpreted carefully and further research is needed. Conclusion: Although further research is warranted, hysteroscopy may be considered as a diagnostic and treatment option for infertile women who have experienced RIF regardless of intrauterine pathologies. This finding enables nurses to educate and support infertile women with RIF prior to IVF/ICSI.

• Clinical and Experimental Reproductive Medicine
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• v.49 no.2
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• pp.149-158
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• 2022

Objective: Optimizing culture media for the incubation of immature oocytes is a vital strategy to increase the oocyte maturation rate during in vitro maturation (IVM) programs. This study evaluated the IVM and fertilization rates of human germinal vesicle (GV) and metaphase I (MI) oocytes using two different maturation media (commercial and homemade) with or without growth differentiation factor 9-β (GDF9-β). supplementation. Methods: Immature oocytes from intracytoplasmic sperm injection (ICSI) cycles were collected and assigned to one of two IVM culture media (commercial or homemade; cleavage-stage base). After maturation, MII oocytes were examined under an inverted microscope for the presence of the polar body, zona pellucida (ZP) birefringence, and meiotic spindle (MS) visualization after maturation in four conditions (commercial or homemade medium, with or without GDF9-β. ICSI was done for matured oocytes, and fertilization was confirmed by the visualization of two distinct pronuclei and two polar bodies. Results: No significant differences were found between the two culture media in terms of the time and rate of oocyte maturation or the rate of fertilization (p>0.05). Growth factor supplementation increased the 24-hour maturation rate for both GV and MI oocytes only in homemade medium. The maturation rate after 24 hours was higher for MI oocytes (p<0.05). Similar results were observed for MS visualization and ZP structure in both types of media (p>0.05). Conclusion: Higher rates of oocyte maturation and fertilization were observed after application of homemade medium supplemented with GDF9-β. Therefore, this combination may be recommended as an alternative for clinical IVM programs.

• Clinical and Experimental Reproductive Medicine
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• v.47 no.4
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• pp.300-305
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• 2020

Objective: The feasibility of a gonadotropin-releasing hormone agonist (GnRHa) trigger in normal responders is still a matter of debate. The aim of this study was to compare the number of mature oocytes, the number of good-quality embryos, and the live birth rate in normal responders triggered by GnRHa alone, GnRHa and human chorionic gonadotropin (hCG; a dual trigger), and hCG alone. Methods: A retrospective cohort study was conducted at the infertility clinic of a university hospital. Data from 200 normal responders who underwent controlled ovarian hyperstimulation and intracytoplasmic sperm injection with a GnRH antagonist protocol between January 2016 and January 2017 were reviewed. The first study group consisted of patients with cycles triggered by GnRHa alone. The second study group consisted of patients with cycles triggered by both GnRHa and low-dose hCG (a dual trigger). The control group consisted of patients with cycles triggered by hCG alone. Results: The groups were comparable in terms of demographics and cycle characteristics. The numbers of total oocytes retrieved and metaphase II oocytes were similar between the groups. The total numbers of top-quality embryos were 3.2±2.9 in the GnRHa group, 4.4±3.2 in the dual-trigger group, and 2.9±2.1 in the hCG group (p=0.014). The live birth rates were 21.4%, 30.5%, and 28.2% in those groups, respectively (p=0.126). Conclusion: In normal responders, a dual-trigger approach appears superior to an hCG trigger alone with regard to the number of top-quality embryos produced. However, no clinical benefit was apparent in terms of live birth rates.