Percutaneous radiofrequency ablation of liver metastases from colorectal cancer: Development of a prognostic score to predict overall survival.

PURPOSE: To develop a model for pretreatment prediction of overall survival (OS) after radiofrequency ablation (RFA) for colorectal liver metastasis (CRLM). METHOD: This retrospective study included 491 patients (median age, 61 years; 348 men) who underwent percutaneous RFA for CRLM between 2000 and 2021. The Kaplan-Meier method was used to estimate OS rates. Independent factors affecting OS were investigated using multivariable Cox regression analysis. Risk scores were assigned to the risk factors and pretreatment prediction models were created using the risk factors. RESULTS: After RFA, the 5-, 10-, and 20-year OS rates were 44 %, 31 %, and 24 %, respectively, and the median OS was 46 months. Multivariate Cox regression analysis showed that a largest tumor size ≥ 2 cm (P<0.001), positive nodal status of primary tumor (P<0.001), carcinoembryonic antigen level > 30 ng/mL (P=0.049), multiple tumors (P=0.008), and T4 stage of the primary tumor (P=0.029) were independently associated with OS. In patients with a single CRLM, tumor diameter (P<0.001), positive nodal status of primary tumor (P=0.001), disease-free interval <12 months (P=0.045), and subcapsular location (P=0.03) were risk factors affecting OS. According to our prediction models, which included the aforementioned risk factors, OS rates progressively decreased as the risk scores increased, with significantly different OS rates between contiguous groups (P<0.001). CONCLUSIONS: Our prediction models can be used as a prognostic stratification tool in patients with CRLM, and can help select those candidates who will benefit most from RFA.

MicroRNAs transfected into granulosa cells may regulate oocyte meiotic competence during in vitro maturation of mouse follicles.

STUDY QUESTION: Do microRNAs (miRNAs) in granulosa cells (GCs) affect oocyte maturation during ovarian follicle development? SUMMARY ANSWER: Sophisticated regulation by miRNAs in ovarian GCs may improve oocyte maturation efficiency during ovarian follicle development. WHAT IS KNOWN ALREADY: The meiotic competence of oocytes depends on the follicle's potential to undergo appropriate maturation and is an important factor in infertility therapies such as IVF. The exact function of the GCs during follicular development remains unknown. STUDY DESIGN, SIZE, DURATION: After in vitro maturation (IVM) and ovulation induction of isolated ovarian pre-antral follicles from 12-day-old female C57BL6 mice (n = 40), miRNA expression in the GCs was compared according to the maturity of the oocyte (metaphase I (MI) versus metaphase II (MII)). The miRNAs, which showed notable different expression, were modulated by transfection during IVM of follicles. MATERIALS, SETTING, METHODS: miRNA expression and candidate target gene expression in GCs of isolated murine ovarian pre-antral follicles were evaluated by real-time PCR after IVM. miR mimics and -inhibitors for selected miRNAs were transfected into the in vitro-maturated follicles, and ovulation, oocyte maturation and fertilization rates were compared. Candidate target gene expressions in GC were evaluated by quantitative PCR and immunohistochemistry using confocal microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: The relative expression of mmu-let-7b (0.78 ± 0.10, P = 0.016), mmu-let-7c (0.78 ± 0.12, P = 0.029), mmu-miR-27a (0.57 ± 0.18, P = 0.016) and mmu-miR-322 (0.59 ± 0.14, P = 0.008) was significantly lower in the GCs of follicles containing MII oocytes compared with those of MI oocytes. Transfection with a mmu-miR-27a-mimic sequence decreased the oocyte maturation rate compared with that for the control (9.4 versus 18.9%, P = 0.042), and transfection with mmu-let-7c-, mmu-miR-27a- and mmu-miR-322-inhibitor sequences increased the oocyte maturation rate by 1.5- to 2.0-folds compared with that for the control (40.6, 31.6, and 30.5%versus 18.9%, P < 0.001, P = 0.013, P = 0.021, respectively). The expression of IGFBP-2 was higher in GCs of MII than in the GCs of MI, and higher in miR-inhibitor transfection groups than in miR-mimic transfection groups and controls. LIMITATIONS, REASONS FOR CAUTION: An in vitro model was used in lieu of an in vivo model because of the ease of performing miRNA transfection in cell culture. However, studies have shown similarities and differences in in vivo versus in vitro cultured follicles. The findings of the present study need to be confirmed using in vivo maturation models and extended to evaluate developmental competence. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that sophisticated miRNA regulation in GCs may improve oocyte maturation efficiency during ovarian follicle development. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A111539). None of the authors has any conflicts of interest to declare.

Ovarian cysts during tamoxifen use may affect the prognostic markers of premenopausal breast cancer.

OBJECTIVES: Only a few studies have suggested the association between ovarian cysts and serum estrogen levels during tamoxifen use. However, increased estrogen levels with ovarian cysts would affect the prognosis of breast cancer; this association has not yet been studied. We aimed to investigate the association between ovarian cysts and prognostic markers in premenopausal breast cancer patients undergoing tamoxifen treatment. METHODS: A retrospective review of 65 premenopausal breast cancer patients who underwent tamoxifen treatment was performed. Serum hormone levels were measured either specifically between cycle days 2 and 5 in menstruating patients or at any time in amenorrheic participants. RESULTS: The study population consisted of premenopausal patients with (n = 23) and without ovarian cysts (n = 42). Serum estradiol (E(2)) levels and tumor markers were not statistically different based on ovarian cyst status. In the subgroup analysis, serum E(2) levels were significantly higher in menstruating women with ovarian cysts, and E(2) levels were positively correlated with serum cancer antigen 15-3 and insulin-like growth factor-1 in these women. CONCLUSIONS: Ovarian cysts during tamoxifen use may affect the markers associated with the clinical course of premenopausal breast cancer.

Polycystic ovary syndrome is not associated with polymorphisms of the TCF7L2, CDKAL1, HHEX, KCNJ11, FTO and SLC30A8 genes.

OBJECTIVE: Insulin resistance is a core feature of polycystic ovary syndrome (PCOS). Recently, genome-wide association studies have reported a number of single-nucleotide polymorphisms (SNPs) with reproducible associations and susceptibilities to type 2 diabetes. We examined the potential association between the diabetogenic genes uncovered in the genome-wide association studies and PCOS in Korean women. DESIGN: Case-control study. PATIENTS: Women with or without PCOS. MEASUREMENTS: DNA samples from 377 patients with PCOS and 386 age-matched controls were genotyped. RESULTS: None of the 12 SNPs in the six genes (KCNJ11, TCF7L2, SLC30A8, HHEX, FTO and CDKAL1) uncovered in the genome-wide association studies were associated with PCOS. For further analysis, the patients with PCOS were divided into two or three subgroups according to genotype, and the associations between the genotypes and insulin resistance or insulin secretory capacity were assessed. No SNPs were significantly associated with HOMA-IR, HOMA (ßcell) (%), or 2-h 75-g oral glucose tolerance test insulin levels in the patients with PCOS; there were no significant associations with other serum hormonal and metabolic markers, such as androgen or glucose levels. CONCLUSIONS: Our results suggest that the six type 2 diabetes-associated genes identified in genome-wide association studies are not associated with PCOS.

Inhibin α gene promoter polymorphisms in Korean women with idiopathic premature ovarian failure.

BACKGROUND: It has been suggested that variations in the inhibin α gene (INHA) may affect the ovarian function of women. This study was performed to investigate whether the genetic polymorphisms of the INHA gene are associated with idiopathic premature ovarian failure (POF) in a Korean population. METHODS: The subjects consisted of 159 idiopathic POF patients and 233 post-menopausal controls. Genotyping for the -16C>T polymorphism was performed by an minor groove binder (MGB) primer/probe Taqman assay, and the -124A>G polymorphism was identified using PCR restriction fragment length polymorphism analysis. Haplotypes were deduced by using the Haploview version 4.1. RESULTS: There were no significant differences in the genotype distributions or allele frequencies of the INHA gene -16C>T and -124A>G polymorphisms between the POF and the control group. Haplotype analysis also showed no significant difference between groups. CONCLUSIONS: The distribution of the INHA gene promoter polymorphisms in a Korean POF population was not significantly different from controls, implying that the INHA gene polymorphisms may not be associated with the risk of idiopathic POF.

Prevalence of elevated glycated hemoglobin in women with polycystic ovary syndrome.

BACKGROUND: Recently, the American Diabetes Association (ADA) has included glycated hemoglobin A1(c) (A1C) level as a component of diagnostic criteria of 'diabetes' or 'increased risk for diabetes'. This study was conducted to examine the prevalence of and risk factors for 'elevated A1C' (≥5.7%) in women with polycystic ovary syndrome (PCOS). METHODS: A1C was measured using an immunoturbidimetric assay, and was evaluated in 154 patients with PCOS and 469 age-matched controls (match ratio of 1-3). All subjects were categorized by BMI (non-obese <25 kg/m(2) and obese ≥25 kg/m(2)), and the prevalence of elevated A1C was also analyzed according to BMI. RESULTS: One-third (31.2%) of the patients with PCOS had elevated A1C. The prevalence of elevated A1C (≥5.7%) was similar in obese women with PCOS and obese controls (23.5 and 20.0%, respectively, P= 1.0) but non-obese women with PCOS (mean age 29.8 ± 5.3 years) had a higher prevalence of elevated A1C than non-obese controls (31.2 versus 6.6%, respectively, P< 0.001). Logistic regression analysis of all subjects showed that the odds that a woman has elevated A1C was 6.7 times higher if she has PCOS (adjusted odds ratio 6.67, 95% confidence interval 3.50-12.70). CONCLUSIONS: The high prevalence of elevated A1C in non-obese patients with PCOS and an increased risk of elevated A1C associated with PCOS suggest that PCOS itself may be associated with abnormal A1C status. Assessing A1C level in young, non-obese patients with PCOS may be a useful new approach to screening for diabetes.

The effect of intracytoplasmic sperm injection on the early hCG level in twin pregnancies.

OBJECTIVES: Since it has been suggested that intracytoplasmic sperm injection (ICSI) might impair the early development of embryos and twin pregnancies have physiologically different aspects from singleton pregnancies, we aimed to investigate the effect of ICSI on the human chrionic gonadotropin (hCG) levels in twin pregnancies. METHODS: A total of 220 clinical pregnancies which underwent controlled ovarian hyperstimulation and in vitro fertilization/ICSI were analyzed retrospectively. RESULTS: In twin pregnancies, the mean number of retrieved oocytes and estradiol (E2) levels on hCG day were significantly higher in ICSI group in spite of lower dose of gonadotropin. The hCG levels according to insemination method did not demonstrate any difference after adjustment for age of patient and partner, BMI, treatment regimens, serum E2 on hCG day, number of oocytes retrieved and date of sampling. CONCLUSIONS: The hCG values according to fertilization methods were not significantly different both in twin pregnancies with adjustment for confounders.

A comparative study on the impact of fresh variables on the success of frozen-thawed embryo transfer cycles using 2PN sibling embryos in women with/without polycystic ovary syndrome.

AIMS: The aim of the present study was to identify the fresh variables that influence the frozen-thawed embryo transfer (FET) outcome using sibling two pronuclei (2PN) embryos in women with polycystic ovary syndrome (PCOS) and non-PCOS women. MATERIAL & METHODS: Fifty-five FET cycles were performed using sibling embryos randomly cryopreserved at 2PN states and basal/cycle characteristics of fresh variables were compared between PCOS and non-PCOS groups according to the success in FET pregnancy: group A (pregnant PCOS); group B (not pregnant PCOS); group C (pregnant non-PCOS); group D (not pregnant non-PCOS). RESULTS: In PCOS patients, higher progesterone level on human chorionic gonadotropin (hCG) day was observed in group A than in group B (0.9 ± 0.0 vs. 0.5 ± 0.3, p = 0.004). In non-PCOS patients who achieved a pregnancy in the fresh cycle, a subsequent FET cycle using sibling 2PN embryos conferred a thirteen times increased chance of achieving pregnancy (OR 13.0; 95% CI, 2.3-74.1). Embryo quality and endometrial maturation were comparable between A and B or C and D. CONCLUSIONS: The success of the fresh embryo transfer (ET)was the most important predictor of pregnancy in FET cycles in the non-PCOS group. The relationship between serum progesterone on hCG day in the fresh cycle and the outcome of subsequent FET would benefit further evaluation in PCOS group.

Effect of trichostatin A on fertilization and embryo development during extended culture of mouse oocyte.

We performed this study to investigate the effect of histone deacetylase inhibition during extended culture of in vitro matured mouse oocytes. In vitro matured mouse (BDF1) oocytes were cultured in vitro for 6, 12, and 24 h, respectively, and then inseminated. During in vitro culture for 6 and 12 h, two doses of trichostatin A (TSA), a histone deacetylase inhibitor, were added (100 nM and 500 nM) to the culture medium and the oocytes were then inseminated. During the 24-h in vitro culture, two doses of TSA were added (100 nM and 500 nM) to the medium and the oocytes were activated with 10 mM SrCl2. After the 6-h culture, the fertilization rate was similar to that of the control group, but the blastocyst formation rate was significantly decreased. After the 12-h culture, both the fertilization and blastocyst formation rates were significantly decreased. After the 24-h culture, total fertilization failure occurred. In the oocytes cultured for 6 and 12 h, the fertilization and blastocyst formation rates did not differ between the TSA-supplemented and control groups. Although extended culture of the mouse oocytes significantly affected their fertilization and embryo development, TSA supplementation did not overcome their decreased developmental potential.

The 8-hydroxydeoxyguanosine concentrations according to hormone therapy and S326C polymorphism of OGG1 gene in postmenopausal women.

BACKGROUND: The 8-hydroxydeoxyguanosine (8-OHdG) is widely used for determination of DNA damage since it is excised from oxidative damaged DNA with endonuclease repair enzymes coded by 8-oxoguanine DNA N-glycosylase gene (OGG1). The present study aimed at investigating whether hormone therapy (HT) may influence on the blood/urinary 8-OHdG levels and whether the level of 8-OHdG is different according to OGG1 S326C polymorphism in postmenopausal women receiving HT. METHODS: In 102 postmenopausal women receiving HT, the 8-OHdG levels were measured in the blood and urine using high performance liquid chromatography (HPLC) before HT and 3 months after HT. The genotyping of the S326C polymorphism of the OGG1 was performed by polymerase chain reaction (PCR) and restriction enzyme fragment length polymorphism (RFLP) analysis. RESULTS: After HT, mean blood 8-OHdG level significantly decreased compared to those before HT (P=0.003), while urinary 8-OHdG level did not show any difference according to HT. Pre-HT level of 8-OHdG was not different according to OGG1 genotypes and similar finding was demonstrated in post-HT 8-OHdG concentration. CONCLUSIONS: These findings imply that hormone therapy can reduce blood 8-OHdG concentration, one of the markers of oxidative damage. Further study is needed to confirm this association in larger population.

Assessment of hirsutism among Korean women: results of a randomly selected sample of women seeking pre-employment physical check-up.

BACKGROUND: The objectives of this study were to define the distribution of the modified Ferriman-Gallwey (mF-G) score in a random group of Korean women and to study any association(s) between hirsutism and endocrine/metabolic markers. METHODS: A single investigator assessed the mF-G score prospectively in 1010 Korean women, who consulted a health-care center as part of a group check-up for employment. Logistic regression models were utilized to test the relationships between the presence of hirsutism and levels of endocrine/metabolic markers. RESULTS: Subjects had mF-G scores ranging from 0 to 19, and 505 subjects (50.0%) had an mF-G score of zero. Of the 1010 subjects, 95.1% had a score at or below six; thus, a score of six or greater represented hirsute women in our population. The most frequently affected site was the upper back, but the most densely affected area was found to be the lower abdomen. Hirsutism was significantly and positively associated with serum levels of total testosterone (T) and hemoglobin A1(c), but negatively associated with those of sex hormone binding globulin (SHBG). In addition, the odds of a woman developing hirsutism were higher for increased total T and HbA1(c), and lower for decreased SHBG. Hirsutism and homeostatic model assessment for insulin resistance were positively associated, but the relationship was not significant after adjusting for age and BMI. CONCLUSIONS: mF-G scores greater that six represent the appropriate diagnostic cutoff for the detection of hirsutism in Korean women. Increased serum total T and HbA1(c,) and decreased SHBG concentrations were associated with the presence of hirsutism.

Red ginseng extract facilitates the early differentiation of human embryonic stem cells into mesendoderm lineage.

Human embryonic stem cells (hESCs) have capacities to self-renew and differentiate into all cell types in vitro. Red ginseng (RG) is known to have a wide range of pharmacological effects in vivo; however, the reports on its effects on hESCs are few. In this paper, we tried to demonstrate the effects of RG on the proliferation and differentiation of hESCs. Undifferentiated hESCs, embryoid bodies (EBs), and hESC-derived cardiac progenitors (CPs) were treated with RG extract at 0.125, 0.25, and 0.5 mg/mL. After treatment of undifferentiated hESCs from day 2 to day 6 of culture, BrdU labeling showed that RG treatment increased the proliferation of hESCs, and the expression of Oct4 and Nanog was increased in RG-treated group. To find out the effects of RG on early differentiation stage cells, EBs were treated with RG extract for 10 days and attached for further differentiation. Immunostaining for three germ layer markers showed that RG treatment increased the expressions of Brachyury and HNF3ß on EBs. Also, RG treatment increased the expression of Brachyury in early-stage and of Nkx2.5 in late-stage hESC-derived CPs. These results demonstrate facilitating effects of RG extract on the proliferation and early differentiation of hESC.

Tri-pronucleated zygotes may occur less frequently in luteinizing hormone activity-added cycles.

OBJECTIVE: This study was performed to evaluate the association between adding luteinizing hormone (LH) activity and the incidence of tripronuclear (3PN) zygotes occurrence. METHODS: The incidence of 3PN and cycle outcomes was compared between recombinant follicle stimulating hormone (rFSH)-only and rFSH with exogenous LH activity groups. These comparisons were performed in gonadotropin releasing hormone (GnRHa, n = 196) and gonadotropin releasing hormone antagonist (GnRHant, n = 182) subgroups, and in in vitro fertilisation (IVF) (n = 243) and intracytoplasmic sperm injection (ICSI) (n = 135) cycles, respectively. RESULTS: The percentage of 3PN was significantly lower in LH activity-added group compared to rFSH-only group (3.6% vs. 5.6%, p = 0.029). Both in GnRHa and GnRHant subgroups, this incidence tended to be lower in LH-supplemented group, although these differences did not reach statistical significance. In IVF cycles, LH activity-added group showed a lower 3PN rate versus rFSH-only group (4.0% vs. 6.7%, p = 0.018). No difference of 3PN rate was found in ICSI cycles. CONCLUSIONS: Supplementation of exogenous LH activity to ovarian stimulation may be associated with lower prevalence of 3PN zygotes in IVF cycles, but not in ICSI cycles.

Effect of maturation on the expression of aquaporin 3 in mouse oocyte.

This study aimed to investigate whether aquaporin 3 (Aqp3) mRNAs are expressed in immature oocytes and altered during in vitro maturation process. Five- to 6-week-old female ICR mice were primed by gonadotropin for 24 and 48 h. Immature oocytes obtained 48 h after priming were also matured in vitro for 17 to 18 h. In vivo matured oocytes were obtained after 48 h priming followed by hCG injection. Total RNAs were extracted from 80 to 150 oocytes in each experimental group, and the levels of Aqp3 mRNA were quantified by real-time reverse transcriptase polymerase chain reaction. The experiments were repeated twice using different oocytes. The Aqp3 mRNA was expressed in immature oocytes, as well as in in vitro and in vivo matured oocytes. The expression level was higher in immature oocytes obtained 48 h after priming (17.2 ± 8.6, mean ± SD) than those with no priming (5.7 ± 0.8) or obtained 24 h after priming (2.5 ± 0.8). The expression of Aqp3 mRNA decreased after in vitro maturation (1.2 ± 0.5), which was similar to in vivo matured oocytes (1.0 ± 0.0). Our work demonstrated that Aqp3 mRNA expression increased during the development of immature oocyte but decreased after completion of in vitro maturation. The results indicate that AQP3 is certainly needed for the acquisition of immature oocytes' full growing potential within antral follicles.

Increased responsiveness may be associated with tripronuclear embryos in both conventional in vitro fertilization and intracytoplasmic sperm injection cycles using gonadotropin-releasing hormone agonist long protocols: a self-matched observational study.

AIMS: In this self-matched observational study, the factors associated with the presence of tripronuclear (3PN) embryos, in conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles using gonadotropin-releasing hormone agonist long protocols, were investigated. MATERIAL & METHODS: Clinical parameters were analyzed in 202 consecutive IVF-IVF or ICSI-ICSI matched cycles. The differences between the former and latter cycles were evaluated and compared according to the presence of 3PN embryos: group A [3PN (-) followed by 3PN (-)]; group B [3PN (-) followed by 3PN (+)]; group C [3PN (+) followed by 3PN (-)]; group D [3PN (+) followed by 3PN (+)]. RESULTS: For the IVF-IVF cycles, the E(2) on human chorionic gonadotropin injection day and the number of retrieved oocytes were increased in the 3PN (+) cycles compared to the 3PN (-) cycles of Groups B (2165.2 ± 1423.3 pg/mL vs 1468.2 ± 796.2 pg/mL, P=0.016; 10.4 ± 9.1 vs 7.2 ± 5.7, P=0.010) and C (2382.7 ± 1214.5 pg/mL vs 1553.0 ± 1119.6 pg/mL, P = 0.004; 13.1 ± 9.1 vs 9.1 ± 7.0, P < 0.001), while these outcome variables did not differ when the former and latter cycles in Groups A and D were compared. These trends were observed in the ICSI-ICSI cycles. CONCLUSIONS: An increased responsiveness, based on the higher E(2) and greater number of retrieved oocytes, may be associated with the presence of 3PN in both conventional IVF and ICSI cycles.

Vesicovaginal fistula following large-loop excision of the transformation zone in a chronic systemic glucocorticoid user.

A 42-year-old woman with a history of a large-loop excision of transformation zone for cervical intraepithelial neoplasia III four years previously visited our outpatient department for cervical intraepithelial neoplasia I that newly detected by colposcopy-directed punch biopsy. Her other medical conditions include systemic lupus erythematosus on daily prednisolone 15 mg during 19 years. After second large-loop excision of transformation zone, delayed vesicovaginal fistula was confirmed by indigo carmine leakage test, computed tomography scan, and cystoscopy. Fistula was primarily repaired with indwelling double-J catheters with anchoring omentum on suture site.

Estrogen receptor {alpha} gene polymorphisms in patients with idiopathic premature ovarian failure.

BACKGROUND: It has been reported that polymorphisms in the estrogen receptor (ER)-alpha gene (ESR1) may be associated with reproductive patterns of women. This study was performed to investigate whether the genetic polymorphisms of the ER-alpha gene are associated with idiopathic premature ovarian failure (POF) in a Korean population. METHODS: The subjects were 126 idiopathic POF patients and 221 post-menopausal controls recruited from university hospitals between 1999 and 2004. Genotyping was performed by MGB primer/probe Taqman assay. Haplotypes were deduced by using the Haploview version 4.1. Bonferroni correction was applied for the correction of multiple testing. RESULTS: There was no significant difference in the allele distribution of the ER-alpha gene (TA)n repeats between the POF and the control group. For the PvuII polymorphism, the POF group showed a higher frequency of TT genotype compared with the controls (41.3 versus 26.3%, P = 0.004, 98.75% CI 1.8-28.2%). No significant difference was found in the distribution of the XbaI polymorphism between the POF and the control group. Haplotype analysis showed that the frequency of TA haplotype was significantly higher in the POF patients compared with the controls (64.7 versus 52.7%, P = 0.002, 98.75% CI 2.4-21.6%). CONCLUSIONS: These findings suggest that the ER-alpha gene polymorphisms may be associated with idiopathic POF.

Anti-Mullerian hormone dynamics during controlled ovarian hyperstimulation and optimal timing of measurement for outcome prediction.

BACKGROUND: Anti-Müllerian hormone (AMH) has been suggested as a marker of ovarian reserve and predictor of ovarian response to controlled ovarian hyperstimulation (COH). Several studies have demonstrated AMH changes during follicular and luteal phases during COH, but not after human chorionic gonadotrophin (hCG) administration. The objectives of this study were to investigate changes in AMH levels during the entire COH cycle and to clarify the regulatory mechanism of AMH secretion. In addition, we analyzed the COH outcome parameters to determine the optimal timing for AMH measurement to predict outcome. METHODS: The study included 74 women who underwent in vitro fertilization (IVF) cycles with a GnRH agonist or antagonist protocol. Serum AMH and inhibin B levels were measured at baseline, Day 5 of stimulation (d5), day of hCG administration (dhCG), day of oocyte retrieval (dOPU) and 14 days after oocyte retrieval (dPO14). Follicular fluid (FF) from dominant follicles upon oocyte retrieval were also analyzed for AMH and inhibin B concentrations. AMH levels were analyzed for changes during the cycle and for correlations with COH outcome parameters. RESULTS: Serum AMH levels decreased progressively during COH until dhCG, then increased on dOPU and further increased on dPO14. Serum and FF AMH levels and dynamic changes were not different between the GnRH agonist and antagonist cycles. Serum AMH levels on every sample day and the FF AMH levels were significantly correlated with outcomes of COH, such as dose of gonadotrophins used, estradiol level on dhCG and number of retrieved oocytes; the strength of the relationship was highest for baseline AMH. CONCLUSIONS: The results of the present study suggest that changes in the hormonal milieu during stimulation and after the LH surge may affect AMH secretion. Serum AMH levels during COH are good markers to predict ovarian response, but the baseline serum level seems to be the most predictive marker.

Effects of adding luteinizing hormone activity to gonadotropin releasing hormone antagonist protocols may differ according to age.

OBJECTIVE: In spite of previous reports on the beneficial effects of adding exogenous luteinizing hormone (LH) activity to gonadotropin releasing hormone (GnRH) antagonist protocols for conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), these effects in various age groups are still controversial. This study was performed to evaluate the clinical efficacy of adding LH activity to GnRH antagonist protocols according to patient's age. METHODS: In this medical record review, responses to controlled ovarian hyperstimulation (COH) and IVF/ICSI outcomes were compared between follicle stimulating hormone (FSH) alone and FSH supplemented with LH activity groups in women < or =35 years (n=135) and those 435 years (n=97), respectively. RESULTS: Estradiol level on hCG day in LH-added group was higher (2.150.6+1.345.1 pg/ml vs. 1.606.2+994.6 pg/ml, P=0.011) in women < or =35 years, while it did not differ in those 435 years. Less oocytes were retrieved in LH-added group of women 435 years (8.1+6.5 vs. 5.7+3.0, P=0.013), however, this figure did not differ in those < or =35 years. Regardless of age, the clinical pregnancy rates were not different between the two groups. CONCLUSIONS: Supplementation of exogenous LH activity to GnRH antagonist protocols affects the COH outcomes. These LH-adding effects may vary according to patient's age.

Clinical efficacy of highly purified hMG versus recombinant FSH in IVF/ICSI cycles: a meta-analysis.

BACKGROUND/AIMS: To compare the effectiveness of highly purified hMG (Menopur) with recombinant FSH (Gonal-F) in IVF/ICSI patients who underwent ovarian hyperstimulation with pituitary suppression. METHODS: A literature search of the National Library of Medicine and the National Institutes of Health (PubMed), Medline and Cochrane Controlled Trials Register was performed using the key words 'highly purified hMG' and 'recombinant FSH.' Only prospective randomized controlled trials were included when they compared IVF/ICSI outcomes after administration of Menopur versus Gonal-F. Five studies met the inclusion criteria and were reviewed. The primary outcome measure was ongoing pregnancy/live birth. RESULTS: Ongoing pregnancy rate per started cycle (RR: 1.10, 95% CI: 0.96-1.26) or per embryo transfer (RR: 1.13, 95% CI: 0.99-1.29), as well as live birth rate per embryo transfer (RR: 1.14, 95% CI: 0.98-1.33), is similar between the Menopur and the Gonal-F group. CONCLUSION: The combined data presented in this meta-analysis do not support a clinical superiority of Gonal-F over Menopur.