Difference in the size of the placenta and umbilical cord between women with natural pregnancy and those with IVF pregnancy.

PURPOSE: The purpose of this study was to compare the sizes of the placenta and umbilical cord in women with natural pregnancy versus those undergoing in vitro fertilization (IVF). METHODS: Overall, 1610 cases of uncomplicated single pregnancies with vaginal delivery at ≥ 37 weeks of gestation were included in this study. The patients were divided into two groups: natural pregnancy group (n = 1453) and IVF pregnancy not including intracytoplasmic sperm injection (ICSI) treatment (n = 157). The groups were compared in terms of gestational week, maternal age, parity, maternal weight gain, prepregnancy maternal BMI, infant weight at birth, infant head circumference, placental weight, cross section of the placenta, cross section of the umbilical cord, insertion site of the umbilical cord, and umbilical cord length. Stepwise selection and multivariate logistic regression were used for statistical analysis to correct the result as an independent factor. RESULTS: There was no difference in the size of the placenta and umbilical cord between women with natural pregnancy and with IVF, but the incidence of velamentous insertion of the cord was significantly increased in women with IVF pregnancy (adjusted odd ratio [AOR] 1.72, 95% confidence interval [CI] 1.08-2.72, p = 0.026). CONCLUSIONS: Although there is no difference in placental weight and cord size, velamentous insertion of the umbilical cord increases in IVF pregnancy and needs careful observation during the delivery process.

Dichorionic triplets following frozen-thawed poor-stage embryo transfer: a report of two cases and a review.

BACKGROUND: We describe two cases of dichorionic triplet pregnancy after a frozen-thawed poor-stage embryo transfer. A 39-year-old and a 41-year-old woman underwent ART treatment. The first patient underwent intracytoplasmic sperm injection (ICSI) at 34 years of age, and two frozen-thawed poor-stage embryos were transferred at 39 years of age with assisted hatching, resulting in a trichorionic triamniotic triplet pregnancy. The second patient underwent ICSI, and two poor-grade blastocysts were transferred followed by assisted hatching, resulting in a dichorionic triamniotic triplet pregnancy. In the first case, the heartbeat of one monozygotic twin fetus had stopped on day 48 post-transfer (9 weeks 2 days), resulting in a dichorionic diamniotic twin pregnancy. A healthy boy and girl were delivered by elective caesarean section at 36 weeks, 5-days gestation. In the second case, the patient underwent selective reduction of the monochorionic twins, resulting in a single pregnancy that was vaginally delivered without any problems at 38 weeks 0-days gestation. SHORT CONCLUSIONS: Numerous factors may be associated with the development of a monochorionic pregnancy; however, controversies still remain. The present morphological grading for embryos is insufficient for inhibiting the development of a monochorionic pregnancy.

Tablet terminals: a useful tool to explain in vitro fertilization treatment.

BACKGROUND: Explanations that involve medical care treatment take time. This also applies to explanations of in vitro fertilization (IVF) in the field of infertility treatment. This is because the cause of infertility differs from couple to couple, and because the explanations must begin with the mechanism of pregnancy. Recently, explanations facilitated by tablet terminals have been used in the field of medicine. In the present study, the efficacy and problems of explanations facilitated by tablet terminals were evaluated and compared with the explanations of IVF facilitated by paper-based pamphlets. METHODS: A total of 249 couples were asked to read a paper-based pamphlet explaining IVF treatment, while 252 couples were asked to view an explanation on a tablet terminal. The patients then answered a seven-item questionnaire. The answers to the questionnaire were based on a three-point scale, and statistical analysis was performed with the Mann-Whitney U test. RESULTS: Patients responded that the explanation facilitated by the tablet terminal was significantly easier to understand for all seven questionnaire items (p <0.05). The answer 'I did not understand' was selected for the items related to 'The treatment fees' (4.8% of answers) and 'Things to take note of, such as consultation times' (6.7% of answers). CONCLUSION: While patients generally did not understand the mechanism of pregnancy, explanations of IVF treatment facilitated by a tablet terminal were found to be more effective than paper-based explanations, although there is room for improvement.

An abdominal ectopic pregnancy following a frozen-thawed ART cycle: a case report and review of the literature.

BACKGROUND: Ectopic pregnancy (EP) occurs in 1% of pregnancies and is reported to be more common in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies. An abdominal ectopic pregnancy (AEP) is a rare form of EP, and there are few reports of an AEP after IVF/ICSI. In this case report, a rare case of AEP after frozen-thawed cycle of ICSI is presented. CASE PRESENTATION: After a frozen-thawed cycle of ICSI, the beta-human chorionic gonadotropin (HCG) level at 4 weeks 0 days of gestation was 3.4 IU/L. Subsequent dysfunctional uterine bleeding was mistaken for menstruation; however, an AEP of 9 weeks with a fetal heart beat was observed by ultrasound. After the AEP was observed by ultrasound, it was extracted laparoscopically. CONCLUSION: A rare case of an AEP, which developed after frozen-thawed cycle of ICSI, presented with a very low serum HCG level. Even if the HCG titer is low, follow-up HCG levels and frequent medical examinations are necessary.

Smiles in the fetal period.

Five-hundred-sixty-eight fetuses were observed at a clinic by using four-dimensional ultrasonography, and 31 fetuses who showed smiles were selected. The range of conceptional age was from 156 days to 214 days. The participants exhibited 51 smiles in 62 min of recording. The average duration of smiles was 3.21s (SD = 1.98). This must be the first study which collected fetal smiles intensively. The age effect on the frequency and duration of fetal smiles is not examined in this study. In comparison with previous studies, the average duration of fetal smiles and that of spontaneous smiles in preterm neonates (3.28s; Kawakami et al., 2008) were not significantly different, but they were significantly longer than that of spontaneous smiles in full-term neonates (1.97s; Kawakami et al., 2006). The fact that fetuses show a lot of smiles makes us reconsider the meanings of spontaneous smiles; fetal smiles must not result from social effects.

Recombinant follicle-stimulating hormone (follitropin alfa) for ovulation induction in Japanese patients with anti-estrogen-ineffective oligo- or anovulatory infertility: results of a phase II dose-response study.

Purpose: To determine the optimal regimen of recombinant human follicle-stimulating hormone (r-hFSH) for ovulation induction (OI) in Japanese women with amenorrhea I or anovulatory infertility. Methods: In this randomized, double-blind, dose-finding study, women aged 20-39 years were enrolled. Patients underwent a chronic low-dose step-up regimen with starting doses of r-hFSH of 37.5 IU (group L; n = 62), 75 IU (group M; n = 62) or 150 IU (group H; n = 60). Primary endpoint was time to achieve a dominant follicle with mean diameter ≥18 mm. Secondary endpoints included percentage of patients producing a dominant follicle ≥18 mm, achieving ovulation, and biochemical pregnancy. Results: Median time to achieve a dominant follicle ≥18 mm was 14 days (group L; 87.7%), 10 days (group M; 98.4%), and 8 days (group H; 94.5%). In group M, ovulation occurred in 95.1% of patients, with pregnancy in 18.0%, compared with 86.0% and 15.8% in group L, and 50.9% and 9.1% in group H, respectively. Twelve patients developed ovarian hyperstimulation syndrome (nine in group H). Most adverse events in groups L and M were mild in severity. Conclusions: A starting dose of 75 IU r-hFSH was associated with a favorable efficacy and safety profile for OI in Japanese women.

Recombinant follicle-stimulating hormone (follitropin alfa) versus purified urinary follicle-stimulating hormone in a low-dose step-up regimen to induce ovulation in Japanese women with anti-estrogen-ineffective oligo- or anovulatory infertility: results of a single-blind Phase III study.

Purpose: We aimed to compare the efficacy and safety of recombinant human follicle-stimulating hormone (follitropin alfa) and purified urinary human follicle-stimulating hormone (urofollitropin) for ovulation induction in Japanese women with anovulatory infertility;also to verify the noninferiority (in terms of ovulation rate) of follitropin alfa versus urofollitropin. Methods: In a Phase III, multicenter, single-blind, parallel-group study, we enrolled 265 Japanese women aged 20-39 years. The patients were menstruating without apparent ovulation or were amenorrheic (with a positive progestin challenge test), and had failed to conceive with anti-estrogen ovulation-induction therapy. The patients underwent a low-dose step-up regimen using follitropin alfa or urofollitropin with a starting dose of 75 IU. The primary endpoint was the proportion of patients who ovulated (mid-luteal serum progesterone ≥5 ng/mL and/or confirmed clinical pregnancy). Secondary endpoints included the proportion of patients with a dominant follicle (≥18 mm) and the duration of stimulation. Results: Ovulation occurred in 79.1% and 82.6% of the patients who received follitropin alfa and urofollitropin, respectively, in the full-analysis set (n = 261), and in 79.2% and 82.5% of the per-protocol set (n = 251). The predefined noninferiority criteria for the primary endpoint were achieved. No significant differences were observed in any secondary endpoint. Treatment-emergent adverse events were reported by a similar proportion of patients in each group (follitropin alfa, 53.5%; urofollitropin, 50.0%). Conclusions: No significant difference in the primary efficacy endpoint (rate of ovulation) was observed between follitropin alfa and purified urofollitropin in women with anovulatory infertility who were menstruating or had progestin-positive amenorrhea. The use of treatment holidays in this study prevents comparison of the data with previous trials that utilized consecutive daily doses.

Analysis of national representative opinion surveys concerning gestational surrogacy in Japan.

OBJECTIVE: Although gestational surrogacy offers several advantages, this procedure has given rise to some ethical and legal issues. We aimed to clarify the factors affecting the attitude of the Japanese toward gestational surrogacy. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Nationwide opinion surveys concerning assisted reproductive technologies (ART) were carried out in 1999 and 2003. Participants included 2568 and 3647 people from the general public surveyed in 1999 and 2003, respectively (1564 people received only the questionnaire, and 2083 people received a questionnaire and brochure about ART). MAIN OUTCOME MEASURE: Multivariate-adjusted odds ratio and 95% confidence interval from logistic regression models for factors affecting the attitude toward gestational surrogacy. RESULTS: In both surveys, approximately half of respondents approved of gestational surrogacy; 20-30% disapproved of the procedure. People with high socioeconomic status clearly expressed their opinion on this issue. A liberal attitude toward gender role promoted approval of gestational surrogacy; a liberal attitude toward family had the opposite effect. CONCLUSION: Our findings suggest that socioeconomic status affects people's expression of their opinion regarding this issue, while attitudes toward this procedure were influenced by individual belief. Considering socioeconomic status and diversity of individual belief is required for further discussion on this topic.

Strong expression of steroid sulfatase in human cumulus cells in patients with endometriosis.

OBJECTIVE: To investigate the localization and expression of steroid sulfatase (STS) in cumulus cells obtained from subjects with and without endometriosis. DESIGN: Case-control study. SETTING: In vitro fertilization program at the Showa University School of Medicine. PATIENT(S): Cumulus cells (142 samples) were obtained from 49 patients for whom IVF was indicated. Some of these samples were taken from cases complicated by endometriosis (35 samples), polycystic ovary syndrome (PCOS; 16 samples), or latent hyperprolactinemia (16 samples). INTERVENTION(S): Immunohistochemical staining for STS. Measurement of STS mRNA expression by real-time polymerase chain reaction (PCR). MAIN OUTCOME MEASURE(S): Expression of STS mRNA and localization of STS. RESULT(S): Steroid sulfatase was localized in the cytoplasm of the cumulus cells, and expression of STS mRNA was observed. The expression level of STS mRNA from patients with endometriosis was significantly higher (11.8-fold) than that of patients without endometriosis. CONCLUSION(S): These results suggest a local steroidal regulation mechanism in cumulus cells. Although the physiological role of STS in cumulus cells remains unclear, STS may be involved in the quality of eggs in patients with endometriosis.

Localization and gene expression of steroid sulfatase by RT-PCR in cumulus cells and relationship to serum FSH levels observed during in vitro fertilization.

BACKGROUND: The purpose of this study was to localize the expression of steroid sulfatase (STS) in cumulus cells and to determine the relationship between STS mRNA expression and the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and progesterone. METHODS: The subject group included 49 women (29 to 44 years old) for whom in vitro fertilization treatment was indicated. All subjects gave informed consent. One hundred fourteen samples of cumulus-oocyte complex (COC) were obtained under microscopic observation. Part of the COC was stained by STS antibody. RNA was extracted by phenol-chloroform method and real-time PCR was performed. Serum of each patient was collected and was measured by ELISA. RESULTS: Some of the cumulus samples were stained by STS antibody. The expression of STS mRNA in all samples was confirmed by quantitative RT-PCR. Although there was no significant correlation between the level of STS mRNA and the serum levels of estradiol, progesterone and LH, there was a statistically significant negative correlation between the level of STS mRNA expression and the serum level of FSH (n = 105, p = 0.018, r = -0.22). CONCLUSION: These results have demonstrated for the first time the expression of STS in cumulus cells by immunohistological stainings and real-time RT-PCR. STS expression in cumulus cells may be related to the control of the local steroidal environment in the oocyte. Serum FSH may control STS mRNA expression from the results of RT-PCR, although the correlation was low.

The influence of inflammatory cytokines on estrogen production and cell proliferation in human breast cancer cells.

Estrogens play important roles in the development of breast cancer. Inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) exist at high concentrations in breast cancer tissue. Although these cytokines are thought to exert some effect on cancer growth, their precise mechanism is still unclear. In the present study, we investigated the effects of inflammatory cytokines on aromatase (Arom) and steroid sulfatase (STS), which are estrogen-producing enzymes, and cell proliferation using human breast cancer cell lines (SK-BR-3, MCF-7). IL-6 and IL-1 beta stimulated the activity of Arom and STS. Estrone sulfate (E1-S) had a stimulus effect on cell proliferation of MCF-7. Although IL-6 did not show significant effect on cell proliferation, cell proliferation was significantly increased when IL-6 and E1-S were simultaneously added to the incubation medium. This cell proliferative effect was apparently stronger than the addition of E1-S alone. Addition of IL-1 beta in the presence of E1-S also significantly enhanced cell proliferation though IL-1 beta alone did not show any effect. These results led us to the hypothesis that inflammatory cytokines such as IL-6 and IL-1 beta regulate proliferation of breast cancer cells through estrogen production by steroid-catalyzing enzymes in the tissue.

Regulation of estrogen activity in human endometrium: effect of IL-1beta on steroid sulfatase activity in human endometrial stromal cells.

We investigated the effect of interleukin 1beta (IL-1beta) on steroid sulfatase (STS) activity and the expression of STS mRNA in human endometrial stromal cells. Endometrial tissue samples were obtained from patients undergoing hysterectomy to remove uterine fibroids. Stromal cells were isolated from the tissue preparation and cultured. IL-lbeta (1 approximately 100 ng/ml) was added into the culture medium and incubated for 24 h. The expression of STS mRNA was measured by competitive RT-PCR. The addition of IL-lbeta at 10 and 100 ng/ml suppressed STS mRNA expression to 55.2 +/- 12.8% and 25.1 +/- 10.9%, respectively, of the control sample to which no IL-lbeta had been added. STS activity was measured by radiolabelled steroid metabolite using thin layer chromatography, and this activity was also significantly suppressed in response to the administration of IL-lbeta in a dose-dependent manner. When IL-1 receptor antagonist (IL-1ra) was added together with IL-1beta to the culture medium, mRNA expression and STS activity were recovered. The present study is the first to demonstrate IL-1beta regulation of STS activity locally in human endometrium. IL-1beta suppressed mRNA and activity of STS in stromal cell culture. This initial demonstration of IL-1beta regulation of STS implies that IL-1beta may control the steroid microenvironment in human uterine endometrium by reducing biologic action of estrogen.