Prolonged pituitary downregulation with gonadotropin-releasing hormone agonist improves the live-birth rate: a retrospective cohort study comparing 3 different protocols.

BACKGROUND: The long protocol has been recognized as the gold standard in controlled ovarian hyperstimulation (COH). However, the full dose of gonadotropin-releasing hormone agonist (GnRH-a) under the prolonged protocol has become increasingly popular in China. This study sought to compare pregnancy outcomes among the following 3 groups: a long protocol group, and 2 types of improved prolonged protocol groups. METHODS: A retrospective cohort study was conducted of 550 patients undergoing fresh embryo transfer (ET). Patients were treated either with the improved prolonged protocol in the follicular phase (Group 1; n=288) or the mid-luteal phase (Group 2; n=143), or the long protocol (Group 3; n=119). The clinical and laboratory outcomes of the 3 groups were compared. RESULTS: The general characteristics of the women in the 3 groups were comparable. On the day on which gonadotropin (Gn) was first administered and on the day on which human chorionic gonadotropin (hCG) was administered, the luteinizing hormone (LH) levels of patients in both Groups 1 and 2 were lower than those of patients in Group 3. The number of oocytes retrieved, fertilized, and cleaved, and the number of high-quality embryos in the 3 procedures were similar. However, the number of transferred embryos, the rate of blastocyst progression, and the rate of implantation differed. The clinical pregnancy rates (CPRs)were significantly higher in the prolonged protocol groups (62.5% and 61.5%) than the long protocol group (48.7%). Further, statistically significant differences in the live-birth rates (LBRs) (56.9% vs. 57.3% vs. 42.9%) were observed. However, no differences in early abortion rates were found. CONCLUSIONS: As a result of pituitary downregulation with GnRH-a, the prolonged groups had better CPRs and LBRs than the long protocol group. The prolonged protocol in the mid-luteal phase was equally effective as that in the early follicular phase in fresh in-vitro fertilization (IVF)/intracytoplasmic sperm injection-embryo transfer (ICSI-ET) cycles. High LH levels on the day of hCG may be a predictor of adverse clinical outcomes.

Effects of Repeated Ovarian Stimulation on Ovarian Function and Aging in Mice.

Controlled ovarian hyperstimulation (COH) is routinely used in the in vitro fertilization and embryo transfer (IVF-ET) cycles to increase the number of retrieved mature oocytes. However, the relationship between repeated COH and ovarian function is still controversial. Therefore, we investigated whether repeated ovarian stimulation affects ovarian aging and function, including follicular development, autophagy, and apoptosis in follicles. Ovarian hyperstimulation in mice was induced by intraperitoneal injection with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Mice subjected to ovarian stimulation once were used as a control group and 10 times as an experimental group. Repeated injections with PMSG and hCG significantly reduced the number of primary follicles compared to a single injection. The number of secondary and antral follicles increased slightly, while the number of corpus luteum increased significantly with repeated injections. On the other hand, repeated injections did not affect apoptosis in follicles associated with follicular atresia. The expression of autophagy-related genes Atg5, Atg12, LC3B, and Beclin1, cell proliferation-related genes mTOR, apoptosis-related genes Fas, and FasL was not significantly different between the two groups. In addition, the expression of the aging-related genes Dnmt1, Dnmt3a, and AMH were also not significantly different. In this study, we demonstrated that repeated ovarian stimulation in mice affects follicular development, but not autophagy, apoptosis, aging in ovary. These results suggest that repetition of COH in the IVF-ET cycle may not result in ovarian aging, such as a decrease in ovarian reserve in adult women.

Gonadotropin-releasing hormone-antagonist up-regulate the proportion of uterine natural killer cells and enhance their toxicity during the implantation window period of mice / 上海交通大学学报（医学版）

Objective: To investigate the effects of gonadotropin-releasing hor-mone-antagonist (GnRH-ant) on the proportion and toxicity of mice uterine nature killer (uNK) cells during implantation window. Methods: Sixteen C57BL/6 mice were randomly divided into GnRH-ant group and control group, with 8 mice in each group. From the 3rd day of the estrous cycle, GnRH-ant (1.5 μg/100 g) was injected intraperitoneally into the mice of the GnRH-ant group for 7 days continuously, and the control group was injected with the same volume of normal saline at the same time point. On the 7th day, the mice of the two groups were injected with human menopausal gonadotropin (40 U/100 g). The next day, they were injected with human chorionic gonadotropin (100 U/100 g) and sacrificed after 48 h. The uterus tissues were taken out for primary digestion to obtain single-cell suspension. Flow cytometry was used to analyze the proportion of uNK cells and the expression levels of toxicity molecules perforin (Pf) and granzyme B (Gz-B). Results: Compared with the control group, the proportion of uNK cells in GnRH-ant group increased (P=0.000), the proliferation level increased (P=0.000), the apoptosis level decreased (P=0.004), and the expression of toxicity molecules Pf (P=0.000) and Gz-B (P=0.034) were up-regulated. Conclusion: GnRH-ant may up-regulate the proportion of uNK cells and enhance their toxicity in the implantation window period of mice.

PPAR signaling pathway in the first trimester placenta from in vitro fertilization and embryo transfer.

Placenta is a temporary critical organ related to fetal development and pregnancy outcomes. And epidemiologic data demonstrate an increased risk of placental abnormality after in vitro fertilization and embryo transfer (IVF-ET). This study aims to explore the molecular mechanism for PPAR signaling pathway in placenta subjected to IVF-ET in the first trimester. Four first trimester placenta samples from double chorionic twins to single reduction in IVF-ET only because of oviducts factors. The other four control placenta samples from double chorionic twin were derived from those unplanned spontaneously conceived pregnancy after the legal termination. Affymetrix HG-U133 Plus 2.0 Array was performed to evaluate the global gene expressions. We confirmed microarray results from 10 significant differential genes using RT-qPCR. And 10 deregulated gene products were stained in the first trimester placenta by immunohistochemistry. These differentially expressed genes in IVF-ET placentas were submitted to functional annotation of clustering tools of bioinformatics resources and gene ontology enrichment analysis. Schematic representation of placental PPAR signaling pathway was labelled by Kyoto Encyclopedia of Genes and Genomes (KEGG). Analysis results of early placental PPAR signaling pathway gene expression from 8 women demonstrated 34 genes with a significant change in expression between IVF-ET and control group, 25 up-regulated; 9 down-regulated. KEGG pathway analysis indicated that IVF-ET manipulation extensively over-activated PPAR signaling pathway. Immune tolerance, trophoblast invasion, syncytia formation, lipid and glucose metabolism, inflammatory response and other complex biological functions were disturbed. RT-qPCR results and proteins staining intensity were consisted with microarray. Placental gene expressions and functions in PPAR signaling pathway were affected by IVF-ET treatment in the first trimester, which may offer a potential mechanism for the pathogenesis of various adverse outcomes during the perinatal period.

The placental transcriptome of the first-trimester placenta is affected by in vitro fertilization and embryo transfer.

BACKGROUND: The placenta is a highly specialized temporary organ that is related to fetal development and pregnancy outcomes, and epidemiological data demonstrate an increased risk of placental abnormality after in vitro fertilization and embryo transfer (IVF-ET). METHODS: This study examines alterations in the transcriptome profile of first-trimester placentas from IVF-ET pregnancies and analyzes the potential mechanisms that play a role in the adverse perinatal outcomes associated with IVF-ET procedures. Four human placental villi from first-trimester samples were obtained through fetal bud aspiration from patients subjected to IVF-ET due to oviductal factors. An additional four control human placental villi were derived from a group of subjects who spontaneously conceived a twin pregnancy. We analyzed their transcriptomes by microarray. Then, RT-qPCR and immunohistochemistry were utilized to analyze several dysregulated genes to validate the microarray results. Biological functions and pathways were analyzed with bioinformatics tools. RESULTS: A total of 3405 differentially regulated genes were identified as significantly dysregulated (> 2-fold change; P < 0.05) in the IVF-ET placenta in the first trimester: 1910 upregulated and 1495 downregulated genes. Functional enrichment analysis of the differentially regulated genes demonstrated that the genes were involved in more than 50 biological processes and pathways that have been shown to play important roles in the first trimester in vivo. These pathways can be clustered into coagulation cascades, immune response, transmembrane signaling, metabolism, cell cycle, stress control, invasion and vascularization. Nearly the same number of up- and downregulated genes participate in the same biological processes related to placental development and maintenance. Procedures utilized in IVF-ET altered the expression of first-trimester placental genes that are critical to these biological processes and triggered a compensatory mechanism during early implantation in vivo. CONCLUSION: These data provide a potential basis for further analysis of the higher frequency of adverse perinatal outcomes following IVF-ET, with the ultimate goal of developing safer IVF-ET protocols.

Analysis of pregnancy outcomes and influencing factors of single embryo transfer and double embryo transfer by in vitro fertilization and embryo transfer / 上海交通大学学报（医学版）

Objective • To compare the pregnancy outcomes between the patients undergoing single embryo transfer and double embryo transfer by in vitro fertilization and embryo transfer, and analyze the influencing factors. Methods • From Jan. 2011 to Jun. 2016, women who underwent single embryo transfer or double embryo transfer with in vitro fertilization and embryo transfer and successfully conceived in Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine were followed up to the pregnancy outcomes. According to the number of embryo transfer, the patients were divided into single embryo transfer group and double embryo transfer group. Univariate analysis (t test, Chi-square test) and multivariate Logistic regression analysis were used to compare the pregnancy outcomes between two groups, and analyze the influencing factors of adverse outcomes. Results • A total of 19 030 patients (98.69%) were followed up to the pregnancy outcomes. Stratified analysis showed that there were significant differences in the composition of pregnancy outcomes (P=0.000) and the number of live births (P=0.000) between two groups. For the neonatal birth quality, the infants born by the patients with single embryo transfer had higher birth weights than those born by the patients with double embryo transfer (P=0.000), and the proportions of newborns with low birth weights and full-term newborns with low birth weights were higher among the patients with double embryo transfer compared to those with single embryo transfer (P=0.000). In addition, there was no statistically significant difference in he incidence of birth defects between the infants born by the patients with single embryo transfer and double embryo transfer. Multivariate Logistic regression analysis showed that the risk of abortion or labor induction among the patients with double embryo transfer was higher than those with single embryo transfer with age, infertility causes and embryo type adjusted (OR=0.88, P=0.025). Conclusion • The risk of adverse pregnancy outcomes is higher among the patients with double embryo transfer than those with single embryo transfer.

Predictive Value of Early Serum Beta-Human Chorionic Gonadotropin Measurements After Cleavage or Blastocyst Embryo Transfers / 中山大学学报(医学科学版)

[Objective]To compare early serum beta-human chorionic gonadotropin (β-hCG) levels after cleavage or blastocyst embryo transfers (ET) in predicting pregnancy outcome.[Methods]A total of 2421 IVF-ET cycles in our center performed from June 2010 to May 2015 and resulted in clinical intrauterine pregnancies were analyzed retrospectively. The predictive value was compared betweenβ-hCG on day 14 after cleavage ET andβ-hCG on day 12 after blastocyst ET.[Results]Serumβ-hCG levels of patients re?sulted in clinical intrauterine pregnancies were significantly higher with blastocyst ET compared with cleavage ET. This significant dif?ference was also existed in patients resulted in miscarriage, ongoing pregnancy (OP) or live birth (LB). However, this significant differ?ence was only existed in frozen embryo transfers. For a frozen cleavage ET, the cut-off value was 475 U/L (sensitivity 79%, specificity 61.3%) in predicting LB. For a frozen blastocyst ET, the cut-off value was 575 U/L (sensitivity 74.9%, specificity 59.2%) in predicting LB.[Conclusion]In frozen embryo transfers, early serumβ-hCG level after blastocyst ET is higher than cleavage ET. The cut-off val?ue in predicting pregnancy outcome is different according to the stage embryo transferred. Early serum β-hCG can effectively predict live birth after blastocyst or cleavage ET.

Correlations of anxiety and depression at different phases with curative outcomes in female patients at IVF-ET Cycle / 现代临床护理

Objective To study the correlations of anxiety and depression at different phases with curative outcomes in female patients at IVF-ET cycle.Methods One hundred and seventeen patients were involved the study using the Self-Rating Anxiety Scale (SAS), Self-Rating Depression(SDS)questionnaires when registered for IVF-ET cycle(T1), one day prior to oocyte retrieval(T2), and 5 to 7 days after embryo transfer(T3).SDS scores and SAS scores were compared between different phases.Logistic regression was used to analyze the correlation of SAS scores with outcome.Results SDS scores of T1, T2 and T3 phases showed no significant differences(all P<0.05).The SAS scores at T2 and T3 were higher than that at T1(all P<0.05), the SAS scores at T2 were higher than that at T3(P<0.05).The SAS scores at T2 in patients achieved clinical pregnancy were significantly lower than that in patients achieved no clinical pregnancy.Logistic regression model showed that lower SAS scores were associated with higher pregnancy rates (P<0.05).Conclusions Anxiety level is the most remarkable one in the phase prior to oocyte retrieval.Low anxiety level prior to oocyte retrieval predicts higher a pregnancy rate.

Hysteroscopic Analysis of IVF-ET Failure in 130 Patients / 中国微创外科杂志

Objective To evaluate the clinical value of hysteroscopy before in vitro fertilization and embryo transfer(IVF-ET).Methods From December 2003 to May 2005,130 patients received hysteroscopy in our hospital because of IVF-ET failure.Their intrauterine diseases were treated by hysteroscopy,and the abnormal tissues were examined pathologically.Results Among the 130 cases,87 had intrauterine diseases(87/130,66.9%) including endometritis in 40(40/130,30.8%),endometrial polyps in 23(23/130,17.7%),intrauterine adhesion in 20(20/130,15.4%),and submucous leiomyoma in 4(4/130,3.1%).In these patients,67 underwent IVF/ICSI or frozen embryo transfer within one year after the hysteroscopy,of which 20 patients achieved pregnancy.The clinical pregnancy rate was about 30%.The other 20 cases did not repeat IVF-ET in 10-20 months after the hysteroscopy,and had no pregnancy without contraception.Conclusion Pre-transfer hysteroscopy is helpful to avoid IVF-ET failure owing to intrauterine diseases.

The clinical efficacy of body mass index as a predictor of in vitro fertilization and embryo transfer outcomes / 대한산부인과학회지

OBJECTIVE: To evaluate the clinical efficacy of body mass index (BMI) as a predictor of in vitro fertilization and embryo transfer (IVF-ET) outcomes. METHODS: Two hundred twenty-three IVF-ET cycles in 164 patients under 37 years using GnRH agonist long protocol were included in this retrospective study. All of the selected cases were divided into two groups by BMI of 24 kg/m2 and these two groups were compared in regard to the outcomes of IVF-ET. RESULTS: There were no significant differences between Group 1 (BMI or =24 kg/m2) in age, basal serum FSH level, estradiol (E2) level and endometrial thickness on hCG day, number of retrieved oocytes and transferred embryos. However, more gonadotropins were used in Group 2 with borderline significance (30.8+/-12.7 ampules vs. 35.4+/-15.3 ampules, p=0.051). The clinical pregnancy rate was significantly lower in Group 2 (25.9% vs. 10.5%, p=0.041) and implantation rate tended to be lower in Group 2 with borderline significance (12.7% vs. 6.8%, p=0.085). CONCLUSION: BMI> or =24 kg/m2 may have a detrimental effect on the IVF-ET outcomes in Korean infertile women, and BMI may be a candidate predictor for IVF outcomes.

Clinical Efficacy and Hormonal Change of GnRH Antagonist in Controlled Ovarian Stimulation for IVF-ET / 대한불임학회지

OBJECTIVES: To evaluate the efficacy of GnRH antagonist cetrorelix in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) and to determine changes in serum hormone concentrations during cetrorelix administration. METHODS: We performed a clinical trial on 30 patients undergoing COH with highly purified follicular stimulating hormone (HP-FSH) and gonadotropin releasing hormone antagonist (GnRHant), cetrorelix. FSH was administrated from day 2 or 3 of cycle with fixed dose and adjusted according to individual response. 0.25 mg of cetrorelix was injected daily subcutaneously from stimulation day 5 until the day of hCG administration. Daily ultrasound monitoring was performed for growing follicles and serum levels of luteinizing hormone (LH), estradiol (E2) and progesterone were measured daily during cetrorelix administration. Up to 4 embryos were transferred. RESULTS: Mean age of enrolled patients was 32.0+/-3.4 years (mean +/-S.D.). All of 30 patients underwent oocyte pick-up, and embryo transfer was done in 28 patients. The total and mean numbers of received oocytes were 196 and 6.5+/-4.7, the number of fertilized eggs was 111, and the fertilization rate was 56.6%. Total duration of FSH administration was 9.2+/-2.2 days and mean of 24.3+/-7.7 ampules of HP-FSH was administered. Total duration of cetrorelix administration was 5.7+/-1.9 days. Serum LH and progesterone levels were maintained in the range of 1.4~2.9 mIU/mL and 0.3~0.6 ng/ mL, which respectively reflected effective prevention of premature LH surge. Clinical pregnancies were achieved in 9 patients, and overall clinical pregnancy rate was 30.0% per oocyte retrieval, and 32.1% per embryo transfer. CONCLUSION: GnRH antagonist is safe and convenient for COH for IVF-ET and effective with optimal pregnancy rate.

Estrogen Receptor Gene Polymorphism (PvuII and XbaI) and Outcomes of Controlled Ovarian Hyperstimulation for In-vitro Fertilization and Embryo Transfer / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to investigate the association of the estrogen receptor alpha gene polymorphism (PvuII and XbaI) with outcomes of controlled ovarian hyperstimulation for in- vitro fertilization and embryo transfer (IVF-ET). METHODS: The PvuII and XbaI in the estrogen receptor gene was analyzed by PCR-RFLP in 189 infertile women undergoing controlled ovarian hyperstimulation for in-vitro fertilization and embryo transfer. Comparisons were done between the three PvuII or XbaI genotypes, concerning the numbers of follicles and oocytes, the ratio of oocytes to follicles, serum estradiol concentrations, total dose of gonadotropins, number of transferred embryos, implantation rate and pregnancy rate. RESULTS: In this study, there was no statistically significant difference in outcomes of controlled ovarian hyperstimulation, except total dose of gonadotropins used among three genotypes of PvuII or XbaI polymorphism. CONCLUSION: These results suggest that the PvuII and XbaI polymorphisms of the estrogen receptor gene are not associated with the outcomes of controlled ovarian hyperstimulation for IVF-ET in Korean infertile women.

Clinical Efficacy of Assisted Hatching with Partial Zona Dissection in Intrauterine Embryo Transfer / 대한산부인과학회잡지

OBJECTIVE: To investigate the clinical efficacy of assisted hatching (AH) with partial zona dissection (PZD) in intrauterine embryo transfer in the patients who failed more than 2 times with standard IVF-ET protocol (Group R), were more than 37 years old (Group A), or had high basal serum FSH levels more than 15 mIU/ml (Group F). METHODS: From January, 1998 to June, 2002, 156 cycles of AH with partial zona dissection were performed in 117 infertile patients in Department of Obstetrics and Gynecology, Seoul National University Hospital. The outcomes of AH were analyzed according to pregnancy rate. RESULTS: The number of oocytes retrieved after controlled ovarian hyperstimulation (COH) was 8.3 +/- 5.2 in 104 cycles of 75 patients who failed more than 2 times with standard IVF-ET protocol (Group I: Groups R, R+A, R+F, and R+A+F), 7.7 +/- 5.0 in 82 cycles of 67 patients who were more than 37 years old (Group II: Groups A, R+A, A+F, and R+A+F), and 7.2 +/- 4.9 in 38 cycles of 30 patients who had high basal serum FSH levels more than 15 mIU/ml (Group III: Groups F, R+F, A+F, and R+A+F). The number of embryos transferred after AH was 4.1 +/- 1.5 in Group I, 3.7 +/- 1.3 in Group II, and 4.0 +/- 1.7 in Group III. The mean cumulative embryo score (CES) was 81.9 +/- 46.5 in Group I, 75.9 +/- 43.0 in Group II, and 75.7 +/- 40.2 in Group III. There were no significant differences in the numbers of oocytes retrieved, embryos transferred and CES among 3 groups. The overall clinical pregnancy rate was 22.4% (35/156) per cycle and 29.9% (35/117) per patient. The clinical pregnancy rate per cycle and per patient was 18.3% (19/104) and 25.3% (19/75) in Group I, 15.9% (13/82) and 19.4% (13/67) in Group II, and 31.6% (12/38) and 40.0% (12/30) in Group III, and there was a significant difference between Group II and Group III. CONCLUSION: AH of human embryos with PZD might be promising for the improvement of pregnancy rates, especially in the patients with the past history of repeated failure, old age, or high basal serum FSH level.

Clinical Efficacy of Reduced Dose GnRH Agonist Long Protocol for Controlled Ovarian Hyperstimulation in IVF-ET Patients with High Basal Serum FSH Level / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinical efficacy of half-dose and further reduced dose GnRH agonist long protocols for controlled ovarian hyperstimulation (COH) in in vitro fertilization and embryo transfer (IVF-ET) patients with high basal serum FSH level. METHODS: One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH level (FSH>10.0 mIU/mL) were included in this retrospective study. Study subjects were assigned in two groups: continuous half-dose GnRH agonist long protocol (Group A, n=63) vs. further reduced dose GnRH agonist long protocol (Group B, n=39) from half-dose at the start of GnRH agonist to 1/3 or 1/4 dose after pituitary suppression. Exogenous FSH or hMG was administered for COH in step-down mode, 4 or less embryos were transferred, and intramuscular progesterone or 8% progesterone gel was used for the luteal support. RESULTS: Serum estradiol (E2) level on hCG day was significantly higher in Group B (1,318.3 +/- 1,120.4 vs. 2,054.9 +/- 1,773.5 pg/mL, p=0.015). The number of transferable embryos was also significantly higher in Group B (2.9 +/- 1.7 vs. 3.7 +/- 2.0, p=0.027). There was no statistically significant difference in the outcomes such as the dose of gonadotropins administered, the number of oocytes retrieved, and the clinical pregnancy rate. CONCLUSION: GnRH agonist long protocol with the reduced dose from half-dose at the start to 1/3 or 1/4 of dose after pituitary suppression may be more beneficial for COH in IVF-ET patients with high basal serum FSH level. Further prospective randomized controlled study in a larger scale will be necessary to confirm this findings.

Clinical Efficacy of Reduced Dose GnRH Agonist Long Protocol for Controlled Ovarian Hyperstimulation in IVF-ET Patients with High Basal Serum FSH Level / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinical efficacy of half-dose and further reduced dose GnRH agonist long protocols for controlled ovarian hyperstimulation (COH) in in vitro fertilization and embryo transfer (IVF-ET) patients with high basal serum FSH level. METHODS: One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH level (FSH>10.0 mIU/mL) were included in this retrospective study. Study subjects were assigned in two groups: continuous half-dose GnRH agonist long protocol (Group A, n=63) vs. further reduced dose GnRH agonist long protocol (Group B, n=39) from half-dose at the start of GnRH agonist to 1/3 or 1/4 dose after pituitary suppression. Exogenous FSH or hMG was administered for COH in step-down mode, 4 or less embryos were transferred, and intramuscular progesterone or 8% progesterone gel was used for the luteal support. RESULTS: Serum estradiol (E2) level on hCG day was significantly higher in Group B (1,318.3 +/- 1,120.4 vs. 2,054.9 +/- 1,773.5 pg/mL, p=0.015). The number of transferable embryos was also significantly higher in Group B (2.9 +/- 1.7 vs. 3.7 +/- 2.0, p=0.027). There was no statistically significant difference in the outcomes such as the dose of gonadotropins administered, the number of oocytes retrieved, and the clinical pregnancy rate. CONCLUSION: GnRH agonist long protocol with the reduced dose from half-dose at the start to 1/3 or 1/4 of dose after pituitary suppression may be more beneficial for COH in IVF-ET patients with high basal serum FSH level. Further prospective randomized controlled study in a larger scale will be necessary to confirm this findings.

In vitro maturation,fertilization and embryo transfer of immature oocytes derived from nature cycles / 重庆医科大学学报

Objective:To investigate the effect of in vitro maturation(IVM),fertilization and embryo transfer of immature oocytes derived from nature cycles in infertility couples.Methods:30 IVF/ICSI-ET cycles were involved in this study.Oocytes retrieval performed after follicle larger than 10 mm and before endogenesis Luteinizing hormone(LH) surge occurrence in nature cycle.Mature oocytes(Metaphase Ⅱ) were inseminated by standard in vitro fertilization(IVF) on the oocytes pick-up day.Immature oocytes(Metaphase I and germinal vesicle stage) were cultured for 24~48 hours and fertilized by intracytoplasmic sperm injection(ICSI) as soon as it developed to Metaphase Ⅱ stage.Embryo transfer was performed 72 h after fertilization.Results:2 of 30 IVM cycles brought no oocytes in this study.113 oocytes were obtained among other 28 oocyte retrieval cycles,74 of which were immature,29 were mature,and 10 were degenerated.60 of 74 immature oocytes developed to MⅡ after IVM(maturation rate 81.08%).6 cases of clinical pregnancy were obtained in the 20 embryo transfer cycles,five of which brought healthy babies(one came from immature oocyte and four came from mature oocyte) and one was abortive.Conclusion:IVM,fertilization and embryo transfer of immature oocytes derived from nature cycles is a feasible treatment for women with infertility.

Influence of Antiphospholipid Antibodies on IVF-ET Outcome in Women Referred for IVF-ET / 대한산부인과학회잡지

OBJECTIVE: The present study was designed to investigate if antiphospholipid antibodies (aPL) could affect the pregnancy outcome in women undergoing in vitro fertilization and embryo transfer (IVF-ET). MATERIALS AND METHODS: From January 1997 to June 2001, 9 women with aPL who underwent IVF- ET were studied. Forty-five women without aPL who underwent IVF-ET served as control. Anticardiolipin antibody (aCL) IgG, IgM, lupus anticoagulant (LA) were assayed with use of standardized enzyme linked immunosorbent assays (ELISA) and dilute Russell's viper venom time (dRVVT) test. Long protocol of gonadotropin-releasing hormone agonist (GnRH-a) was used for controlled ovarian hyperstimulation (COH) in all patients. Statistical analysis was performed using Student's t-test, Fisher's exact test, and x2 test as appropriate. Statistical significance was defined as p<0.05. RESULTS: There were no significant differences between the study and control groups in patient characteristics such as age, infertility duration, hormonal profile, cause of infertility and number of previous IVF attempts. There were also no significant differences between two groups with respect to clinical response to COH and IVF results such as number of retrieved oocytes, fertilization rate, number of embryos frozen and number of embryos transferred. The clinical pregnancy rate per cycle seemed to be higher in the study group than in the control group (25.0% vs 14.9%), however, the difference was not statistically significant. Miscarriage rate per clinical pregnancy was significantly higher in the study group at 67.0% (4/6) compared with 29.4% (5/17) in the control group. Delivery rate per clinical pregnancy was significantly lower in the study group at 16.7% (1/6) compared with 58.8% (5/17) in the control group. CONCLUSION: Women with aPL undergoing IVF-ET may have similar IVF outcome compared with women without aPL, except miscarriage rate per clinical pregnancy.

The Predictive Value of a Single Serum Beta Human Chorionic Gonadotropin Level in Pregnancies Achieved by Intrauterine Insemination and In Vitro Fertilization-Embryo Transfer Program / 대한산부인과학회잡지

OBJECTIVE: To clarify specific serum beta-human chorionic gonadotropin (beta-hCG) levels on 11 days after intrauterine insemination (IUI) and in vitro fertilization-embryo transfer (IVF-ET) that could predict live birth. METHODS: Three hundred ninety-two pregnancies resulting from IUI and IVF-ET procedures between January 1, 1997 and December 31, 2000 were evaluated. Serum quantitative beta-hCG levels were measured 11 days after IUI or ET using standard immunoradiometric assays. Pregnancy outcomes were categorized as spontaneous abortion, biochemical pregnancy, ectopic pregnancy, singleton live birth, or multiple live birth. Statistical analyses were performed by analysis of variances, and Student's t-test. The sensitivity and specificity of serum beta-hCG level for predicting live birth were plotted using receiver-operator-characteristic (ROC) curve. RESULTS: The multiple live birth group has significantly higher serum beta-hCG level among the different pregnancy outcome groups. The beta-hCG level on the eleventh day after IUI and IVF-ET was significantly higher in the live birth group than the non viable pregnancy group. At a threshold level of 65 mIU/ml, the serum beta-hCG level on the eleventh day after IUI had a positive predictive value of 78.9% in predicting live birth with 95% specificity. At a threshold level of 115 mIU/ml, the serum beta human chorionic gonadotropin level on the eleventh day after ET had a positive predictive value of 92.1% with 95% specificity. CONCLUSION: These data suggest that serum beta-hCG level on 11 days after IVF-ET could be a reliable indicator predicting pregnancy outcome.

Cumulative Pregnancy Rate of In Vitro Fertilization and Embryo Transfer With Intracytoplasmic Sperm Injection / 대한산부인과학회잡지

OBJECTIVE: To compare the clinical outcomes between Day 2 and Day 3 embryo transfer(ET) groups in in vitro fertilization and embryo transfer(IVF-ET) with intracytoplasmic sperm injection(ICSI). METHODS: From May, 1997 to December, 1998, 174 cycles of IVF-ET with ICSI were performed and classified into two groups: Day 2 ET group(n=134) and Day 3 ET group (n=40). In Day 3 ET group, embryos fertilized after ICSI were cultured in vitro for further 24 hours in M3 media. RESULTS: There were no significant differences in the age and BMI of patients, basal serum FSH level, protocol of controlled ovarian hyperstimulation(COH), indication of ICSI, and source of sperm for ICSI between two groups. Only the number of the previous failed IVF-ET cycles was significantly higher in Day 3 ET group(p<0.05). Serum E2 level on hCG day, the numbers of oocytes retrieved after COH, oocytes fertilized after ICSI, and embryos transferred, and the rates of fertilization, cleavage, and implantation showed no significant differences. However, cumulative embryo score(CES) was significantly higher in Day 3 ET group(p<0.05). Although there were no significant differences in the rates of pregnancy per ET, spontaneous abortion, and live birth, the rates of biochemical and multiple pregnancy were significantly higher in Day 3 ET group(p<0.05). CONCLUSIONS: In IVF-ET with ICSI, the relatively higher CES may contribute to the higher risk of multiple pregnancy in Day 3 ET group, compared with the conventional Day 2 ET group.

Cumulative Pregnancy Rate of In Vitro Fertilization and Embryo Transfer With Intracytoplasmic Sperm Injection / 대한산부인과학회잡지

OBJECTIVE: To evaluate the cumulative pregnancy rate(CPR) of in vitro fertilization and embryo transfer(IVF-ET) with intracytoplasmic sperm injection(ICSI). METHODS: Medical records of 260 infertile patients undergoing 519 cycles of IVF-ET with ICSI from January, 1994 to December, 1999 were retrospectively reviewed. The CPR beyond 12 weeks of gestation was estimated by Kaplan-Meier method. The CPRs were compared by log-rank test between groups divided by age of patients, indication of ICSI, and method of sperm retrieval for ICSI. RESULTS: As 70 patients achieved an on-going pregnancy after IVF-ET with ICSI, the PR was 26.9% per patient and 13.5% per cycle. The overall CPR was 54.9% after 6 cycles of IVF-ET with ICSI. As expected, age had a significant strong effect on the CPR; CPRs afer 4 cycles of ICSI were 61.8% in the age group of 30 years(n=81), 43.7% in 31-35 years(n=106), and 15.3% in 36 years(n=73). There was no significant difference in the CPR between abnormal semen analysis group(n=184) and prior low fertilization rate group(n=66). In abnormal semen analysis group, the CPR of surgically retrieved sperm subgroup(n=60) was not significantly different from that of ejaculated sperm subgroup(n=124). CONCLUSIONS: The CPR of IVF-ET with ICSI was presented, and it could be of much help in the clinical counseling of IVF-ET patients. ICSI technique could be used successfully for IVF-ET in infertile couples who had the male factor infertility or the past history of low fertilization rate in the previous cycles.