Association between ultrasonographic parameters of Cesarean scar defect and outcome of early termination of pregnancy.

OBJECTIVE: To determine whether Cesarean scar defect (CSD) parameters assessed by transvaginal sonography (TVS) might affect the outcome of early termination of pregnancy (TOP) with mifepristone-misoprostol. METHODS: This was a retrospective review of 183 women with previous Cesarean delivery who received oral mifepristone and misoprostol for TOP. A successful TOP was defined by the absence of an intrauterine gestational sac, with no need for surgical intervention. CSD was diagnosed by TVS in the presence of a hypoechogenic indentation within the myometrium of the lower uterine segment at the site of a previous Cesarean incision. Women were analyzed in three subgroups according to size of defect (ratio of residual myometrial thickness over the defect to adjacent myometrial thickness < 30%, 30%-70% and > 70%). RESULTS: Of the 183 women, 43 (23.5%) had failure of TOP. Fifty-nine (32.2%) had CSD detectable at TVS, and these women had a higher failure rate of TOP than did those without CSD (38.9% vs 16.1%; P = 0.001). CSD was associated significantly with failure of TOP (odds ratio, 3.32 (95% CI, 1.64-6.75)). The TOP failure rates in relation to defect size in the myometrial thickness ratio < 30%, 30%-70% and > 70% subgroups were 57.1%, 25.0% and 18.2%, respectively. There was a linear trend in failure rate across these ratios (Cochran-Armitage trend test; P = 0.015). CONCLUSIONS: Women with CSD are at increased risk of failed TOP. Women with a defect in which the residual myometrial thickness was < 30% of the adjacent myometrial thickness tended to have a greater chance of failed TOP. CSD detected at TVS is of clinical relevance in counseling women with a history of Cesarean delivery who are considering TOP. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

A higher anti-Müllerian hormone level is associated with an increased chance of pregnancy in patients undergoing controlled ovarian stimulation and intrauterine insemination.

Anti-Müllerian hormone (AMH) level has been found to be a useful marker of ovarian reserve, and a predictor of poor and hyper-responses in patients undergoing controlled ovarian stimulation (COS). The study aimed to determine the association of serum AMH level with achieving pregnancy in patients undergoing COS with intrauterine insemination. The cross-sectional study investigated 204 patients who underwent COS with intrauterine insemination at the Obstetrics and Gynecology Department of Taipei Medical University Hospital, from January 2011 to March 2012. The medical records of these patients were reviewed, and serum AMH levels were evaluated for association with successful clinical pregnancy. The AMH level in the patients who achieved clinical pregnancy was significantly higher than in patients who did not (median 2.7 vs 2.0 ng/ml, p = 0.005). Controlling for factors affecting infertility, AMH level had a significant independent influence on outcome; a higher AMH level was associated with a decreased risk of a non-pregnant outcome (odds ratio, OR = 0.895, p = 0.026). In patients undergoing COS and intrauterine insemination, a low AMH level is associated with a decreased chance of a clinical pregnancy, and this association remains irrespective of the presence or absence of endometriosis.

Factors affecting reflex pelvic floor muscle contraction patterns in women with pelvic floor disorders.

OBJECTIVE: To explore factors affecting the presence of two reflex pelvic floor muscle contraction (PFMC) patterns in women with pelvic floor disorders. METHODS: This was a retrospective analysis of pelvic floor ultrasonography and urodynamic data for 667 consecutive symptomatic women with pelvic floor disorders. We identified on ultrasonography the presence or absence of two reflex PFMC patterns, anorectal lift (ARL) and inward clitoral motion (ICM), preceding or occurring during coughing, and evaluated their associations with possible factors affecting reflex PFMC reactivity, including patient demographics, pelvic organ prolapse stages, ultrasonography findings and urodynamic data. RESULTS: Of the 667 women, 560 (84.0%) clearly demonstrated reflex ARL and 536 (80.4%) demonstrated ICM. There were significant differences in age (P < 0.001), parity (P = 0.033) and menopausal status (P = 0.005) between women with and those without reflex ICM before or during coughing. The multivariable logistic regression model showed that age was the only independent factor associated with presence of reflex ICM (odds ratio, 0.93 (95% CI, 0.88-0.99), P = 0.017). In contrast, no significant differences were noted between women with and without reflex ARL. CONCLUSIONS: Increasing age is negatively associated with the presence of reflex ICM during coughing in symptomatic women with pelvic floor disorders.

Impact of two reflex pelvic floor muscle contraction patterns on female stress urinary incontinence.

PURPOSE: To explore the impact of two reflex pelvic floor muscle contraction patterns during coughing on incontinence severity and incontinence-related quality of life in women with stress urinary incontinence (SUI). MATERIALS AND METHODS: A total of 208 women with the symptomatic and urodynamic evidence of SUI and 126 women with no experience of urinary incontinence were recruited in a 5-year period. During hard coughs, reflex pelvic floor muscle contraction was detected using introital ultrasound and two reflex contraction patterns were recognized: an inward clitoral motion and a superior-anterior anorectal lift. The assessment of incontinent severity and impact of quality of life included 1-hour pad tests and short forms of the Urogenital Distress Inventory and the Incontinence Impact Questionnaire. RESULTS: There is no significant difference in the demographics and the distribution and concordance of two reflex contractions between women with or without urinary incontinence. Neither type of reflex contraction during coughing was identified in 14 incontinent women (7%) and 5 continent women (4%). The concordant rate for synchronous activities of both reflex contractions during coughing was 80% (167) and 81% (102) for incontinent and continent women, respectively. Incontinent women without clitoral reflex motion had significantly greater incontinent severity on 1-hour pad tests (p = 0.018) and higher sum scores of the short form of Incontinence Impact Questionnaire (p = 0.026). By contrast, incontinent women with and without reflex anorectal lifts had similar incontinence severity and impact. CONCLUSION: In women with SUI, loss of clitoral reflex motion is associated with worse incontinent severity and impact.

Impact of concomitant anterior vaginal reconstructive surgery on transobturator suburethral tape procedures.

OBJECTIVE: To explore the functional and morphological impact of concomitant anterior vaginal reconstructive surgery on outcome of transobturator suburethral tape (TOT) procedures. METHODS: This was a retrospective review and analysis of data from 196 women who had undergone a TOT procedure with or without concomitant anterior vaginal reconstructive surgery during a 30-month period. Retrieved data included clinical information and ultrasound findings. Ultrasound examinations assessed the tape location and tape tension at rest, on straining and during coughing. Ultrasound parameters representing tape location comprised the sagittal tape-symphysis pubis distance, sagittal tape-symphysis pubis angle and tape percentile (an indication of tape position along the urethra with respect to urethral length); those representing tape tension included urethral encroachment, sagittal tape-urethra distances at the upper end, central point and lower end of the tape and axial urethral central echolucent area at the center of the tape. RESULTS: Of the 196 women, 117 had undergone a TOT procedure without concomitant anterior vaginal surgery (Group 1), 44 had undergone TOT placement with anterior colporrhaphy (Group 2) and 35 had undergone TOT placement with a transobturator vaginal mesh procedure (Group 3). At the 3-month follow-up, functional outcomes as well as resting and dynamic ultrasound findings were similar between women following TOT procedures without (Group 1) and with (Groups 2 and 3) concomitant anterior vaginal surgery. However, a significantly higher rate of urethral encroachment at rest was noted in Group 2. CONCLUSIONS: Concomitant anterior vaginal reconstructive surgery neither aggravates the functional outcome nor affects the ultrasound findings of TOT procedures.

Correlation of tape location and tension with surgical outcome after transobturator suburethral tape procedures.

OBJECTIVE: To explore, using 4D ultrasound, the importance of location and tension of transobturator sub- urethral tape (TOT) with respect to surgical outcome. METHODS: Enrolled into the study were 56 women who had undergone TOT placement in the treatment of urodynamic stress incontinence. Tape location and tension were assessed by 4D ultrasound with the women at rest, during straining and during coughing. Ultrasound parameters representing tape location included the sagittal tape-symphysis pubis distance (sTSD), sagittal tape-symphysis pubis angle (sTSA) and tape percentile (an indication of tape position along the urethra with respect to urethral length), while those representing tape tension included urethral encroachment, sagittal tape-urethra distances at the upper end (sTUDu), center (sTUDc) and lower end (sTUDl) of the tape and axial urethral central echolucent area at the tape center (aUCEAc). RESULTS: In women in whom the tape procedure had been successful, during increased intra-abdominal pressure sTSA and the incidence of urethral encroachment increased, while sTUDu, sTUDc, sTUDl and aUCEAc decreased. Compared with those reporting no stress urinary incontinence (SUI) symptoms, women who reported SUI postoperatively had lower tape percentile. Women with SUI postoperatively demonstrated no manifestation on ultrasound of urethral encroachment at rest or during increased intra-abdominal pressure. Women with postoperative overactive bladder (OAB) symptoms had shorter resting sTSD and larger resting sTSA than did women without OAB symptoms. Women reporting postoperative de novo or worsening voiding difficulty had larger resting sTSA and higher incidence of urethral encroachment at rest than did women without this difficulty. CONCLUSIONS: Both tape location and tape tension are associated with surgical outcome of TOT procedures. Assessment of tape location and tension can be achieved using 4D ultrasound.

Functional and morphological differences following Monarc and TVT-O procedures.

OBJECTIVE: To explore function of the lower urinary tract and morphology of tape and urethra following Monarc or TVT-O suburethral tape placement for urodynamic stress incontinence (USI). METHODS: We recruited prospectively women undergoing either Monarc or TVT-O placement for USI. Before and 3 months after the procedure, participants were evaluated by a question-directed interview, the measures of Sandvik Incontinence Severity Index (SISI), Incontinence Bother Scale (IBS), Ingelman-Sundberg Score (ISS) and short forms of Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7), physical examination, a cough stress test and 4D ultrasound investigation. The primary outcome was participants' responses to clinical assessments and the secondary outcome was ultrasound findings. RESULTS: A total of 67 women with Monarc procedures and 60 women with TVT-O procedures completed the survey both preoperatively and 3 months postoperatively. There were significant improvements in scores of SISI, IBS, ISS, UDI-6 and IIQ-7 after both Monarc and TVT-O procedures. At the 3-month follow-up, both procedures had similar success rates, SISI scores, IBS scores, ISS scores, UDI-6 scores and IIQ-7 scores, and similar incidences of postoperative voiding difficulty and overactive bladder symptoms. After Bonferroni correction, all ultrasound parameters representing tape location, tape tension and urethral mobility were similar between the two procedures. CONCLUSIONS: At short-term follow-up, Monarc and TVT-O procedures are comparable in both functional outcome of the lower urinary tract and morphology on ultrasound as assessed by parameters representing tape location, tape tension and urethral mobility.

Reliability of a new method for assessing urethral compression following midurethral tape procedures using four-dimensional ultrasound.

OBJECTIVES: To evaluate the intra- and interobserver reliability of a new method of assessing resting and dynamic urethral compression after midurethral tape procedures using three- and four-dimensional (3D and 4D) ultrasound. METHODS: Thirty-one women who had undergone transobturator midurethral tape procedures at Cathay General Hospital were enrolled in the study and 4D ultrasound was performed pre- and postoperatively. Preoperative ultrasound assessment included measurement of the urethral central echolucent area (UCEA) in the axial plane. Postoperative ultrasound assessment included measurement of the tape-urethral distance (TUD) in the sagittal plane as well as UCEA and tape angle in the axial plane (ATA). The TUD was measured at the upper end (TUDu), central point (TUDc) and lower end (TUDl) of the tape. All pre- and postoperative ultrasound assessments were performed in women at rest, on maximum straining and during strong coughing. 4D ultrasound volume datasets were stored digitally and analyzed offline by two independent investigators blinded to clinical data and to each others' measurements. Intra- and interobserver reliability were evaluated using the intraclass correlation coefficient (ICC). RESULTS: There were significant reductions in TUDc, TUDl and UCEA during increased intra-abdominal pressure. ICC values for the measurement of TUD at rest, on straining and during coughing demonstrated very good reliability. ICC values for the pre- and postoperative measurement of UCEA at rest, on straining and during coughing demonstrated good to very good reliability. ICC values for the measurement of ATA at rest, on straining and during coughing demonstrated fair to good reliability. CONCLUSIONS: 4D ultrasound can be used to obtain measurements with good reliability in the assessment of urethral compression.

Effect of cetrorelix dose on premature LH surge during ovarian stimulation.

Previous studies have shown that ovarian stimulation with clomiphene citrate (CC), human menopausal gonadotrophin (HMG), and multiple-dose gonadotrophin-releasing hormone (GnRH) antagonist is associated with a high rate of premature LH surge. This study assessed whether administration of the GnRH antagonist cetrorelix at an incremental dose or at a high dose (0.5mg) from the start could prevent premature LH surge. Couples with male factor or unexplained infertility who were going to undergo intrauterine insemination were randomized into two stimulation protocols. All women were stimulated with CC and HMG. In protocol A, cetrorelix was given at 0.25 mg per day when the leading follicles reached 14 mm, and increased to 0.5 mg when the leading follicles were 16 mm. With protocol B, cetrorelix was given at 0.5 mg per day when the leading follicles reached 14 mm. The primary outcome measure was the incidence of premature LH surge. Premature LH surge occurred in 21.6% of patients undergoing protocol A, and in 18.9% of patients undergoing protocol B. Cetrorelix at incremental dose or at 0.5 mg per day does not prevent premature LH surges associated with the CC/HMG/multiple-dose cetrorelix stimulation protocol.

Recurrent retroperitoneal myxoid liposarcoma during pregnancy: a case report and literature review.

Retroperitoneal liposarcoma in pregnancy is rare, and only a few cases of primary liposarcoma during pregnancy have been reported. To the best of our knowledge, there is no published report of retroperitoneal liposarcoma that was previously treated and recurred during pregnancy. Our patient was diagnosed with a pelvic mass on ultrasound at 12-weeks' gestation. The mass was found to be a retroperitonal, well-differentiated myxoid liposarcoma and was radically excised at the time of cesarean delivery at 36-weeks' gestation. However, the tumor recurred soon and progressed rapidly, and the patient eventually died of the disease. A thorough sonographic investigation and timing of surgery may be critical in terms of finding a surgically resectable lesion and leading to a more favorable prognosis.

Assessment of changes in utero-ovarian arterial impedance during the peri-implantation period by Doppler sonography in women undergoing assisted reproduction.

OBJECTIVE: To investigate changes in utero-ovarian blood flow during the peri-implantation period and their significance in successful embryo implantation. METHODS: A prospective longitudinal study was conducted in 317 women undergoing in-vitro fertilization-embryo transfer (IVF-ET) treatment. All of them had at least one good-quality embryo for transfer on the second or third day after oocyte retrieval. Measurement of endometrial thickness and color flow imaging with pulsed waveform analysis of uterine and ovarian arteries were performed before ET and 5-6 days after ET. RESULTS: There were no significant differences in the age of patients, duration of infertility or number of embryos transferred between women who became pregnant (n = 91) and those who did not (n = 226). There was no difference in mean endometrial thickness between the two groups before ET, while a thicker endometrium was found in women who had conceived compared with those who had not 5-6 days after ET (P = 0.02). Mean uterine arterial resistance index (RI) and pulsatility index (PI) values were significantly lower in the pregnant than in the non-pregnant group before ET (P = 0.04 and P = 0.003, respectively), but no significant differences were found between the two groups 5-6 days after ET. In contrast, the mean ovarian arterial RI and PI values were similar between the two groups before ET, yet the pregnant group showed significantly lower RI and PI values compared with the non-pregnant group 5-6 days after ET (P = 0.002 and P = 0.01, respectively). A significantly higher peak systolic velocity (PSV) of intraovarian vessels was also noted in the pregnant group 5-6 days after ET. CONCLUSION: Different utero-ovarian blood flow changes during the peri-implantation period occur in conception and non-conception cycles in women following IVF. Doppler assessment of uterine arterial resistance can help to determine a time interval within the menstrual cycle that is of optimal endometrial status for embryo implantation in assisted conception programs. Delay in achieving adequate uterine perfusion during the temporal window of embryo implantation may have an impact on endometrial receptivity.

Cytologic and histologic review of atypical glandular cells (AGC) detected during cervical cytology screening.

This article is to determine the clinical significance and underlying pathology among patients with atypical glandular cells (AGC) identified during cervical Papanicolau (Pap) smear screening. AGC slides were searched from 51,412 computerized files of the cytology laboratory of Mackay Memorial Hospital during a 29-month period. The results of clinical evaluations were reviewed and an experienced gynecologic cytopathologist who was not involved in the original cytologic diagnosis and was not aware of the clinical results of the follow-up examinations rechecked all AGC slides. We used the z score to determine whether different results were achieved after the gynecologic cytopathologist rechecked the slides. We further analyzed all slides with different cytologic diagnoses and compared results with the histologic diagnoses. Forty-nine cases were initially identified as AGC. Among these, 29 were reviewed and identified as AGC again, and the result of biopsies revealed that they were all chronic cervicitis, ie, negative for malignancy or premalignancy. The other 20 cases were reviewed and diagnosed as non-AGC. Among the results of cytologic examinations, seven had inflammation, two had atypical squamous cells of undetermined significance (ASC-US), ten had high-grade cervical intraepithelial neoplasia (CIN), and one had adenocarcinoma. The results of histologic diagnosis included eight cases with normal tissue, two with CIN grade 1, eight with high-grade CIN, one with microinvasive squamous cell carcinoma, and one with adenocarcinoma. Histologic results revealed 20.4%1 (10/49) and 50% 1(10/20) at initial cytologic diagnosis of AGC and expert-reviewed non-AGC, respectively, which were finally at least high-grade CIN. According to the gynecologic cytopathologist's diagnosis, 59.2%1 (29/49) of cases would have eliminated unnecessary histologically diagnostic procedures. In conclusion, clinicians should be careful about the significance of the cytologic diagnosis of AGC, because there may actually be an underlying pathology, which can be identified by a pathologist who is an expert in gynecologic cytopathology. The interobserver variation in diagnosing AGC favors specialized training in gynecologic cytopathology. In addition, prompt diagnostic interventions, including colposcopy, endocervical curettage, and/or endometrial biopsy, should be performed after confirmation of the diagnosis of non-AGC by an experienced gynecologic cytopathologist.

The hyperaggregability of platelets from normal pregnancy is mediated through thromboxane A2 and cyclic AMP pathways.

There is substantial evidence of increased platelet reactivity in vivo and in vitro during pregnancy, with the risk of developing pre-eclampsia. In this study, platelet function was studied during 28-40 weeks of gestation in a group of women who remained normotensive and in a group of nonpregnant female controls. Platelet aggregation stimulated by thrombin and adenosine diphosphate was markedly enhanced in washed platelets from pregnant subjects. Thrombin (0.04 U/ml)-evoked increases in intracellular Ca+2 mobilization of Fura 2-AM-loaded platelets were also enhanced in pregnant subjects. The binding of fluorescein isothiocyanate (FITC)-triflavin (2 microg/ml) to the glycoprotein IIb/IIIa complex in thrombin-activated platelets did not differ significantly between the nonpregnant and pregnant groups. Thromboxane A2 (TXA2) formation in both resting and thrombin-activated platelets from pregnant subjects was significantly greater than from nonpregnant subjects. Levels of cyclic adenosine monophosphate (cAMP) in both resting and prostaglandin E1-treated platelets (10 micromol/l) from pregnant subjects were significantly lower than those from nonpregnant subjects. There were no significant differences between nonpregnant and pregnant subjects in platelet cAMP levels in the presence of imidazole (600 micromol/l) and indomethacin (500 micromol/l). Intracellular pH values in platelets were measured spectrofluorometrically using the fluorescent probe, BCECF-AM. The increase in intracellular pH stimulated by thrombin (0.04 U/ml) in pregnant subjects was markedly greater than that in observed nonpregnant subjects. We conclude that the agonist-induced hyperaggregability of platelets in normal pregnancy may be due, at least partly, to stimulation of the Na+/H+ exchanger and subsequently to elevated intracellular Ca+2 mobilization, and then to increased TXA2 formation and a lowered level of cAMP, which leads to further increases in intracellular Ca+2 mobilization, and finally to enhanced platelet aggregation.

Antigonadotropic action of adenosine triphosphate in human granulosa-luteal cells: involvement of protein kinase Calpha.

The presence of P2U purinoceptor in human granulosa-luteal cells (hGLCs) indicates a potential role of ATP in regulating ovarian function. In this study an inhibitory effect of ATP on hCG-induced cAMP production was observed. Extracellular ATP has been shown to activate protein kinase C (PKC) after binding to a purinoceptor. To understand the role of PKC in mediating ATP action, hCG-stimulated cAMP level was examined in the presence of the PKC activator, 1 micromol/L phorbol 12-myristate 13-acetate (PMA), or the PKC inhibitor, 1 micromol/L staurosporin or 1 micromol/L bisindolylmaleimide I. PMA, like 10 micromol/L ATP, significantly reduced hCG-evoked cAMP production. In addition, the inhibitory effect of ATP was reversed by staurosporin and bisindolylmaleimide I. To further investigate the involvement of PKC isoforms in mediating the inhibitory effect of ATP, the presence of PKC isoforms in cultured hGLCs was examined by Western blot using monoclonal antibodies against specific isoforms. Translocation of PKC isoforms from cytosolic fraction to membrane fraction was studied to identify the active PKC isozymes subsequent to ATP treatment. The change in PKC isoform in PKC-depleted cells (achieved by exposure to PMA for 18 h) was also examined. Our results demonstrated the presence of PKCalpha, -delta, -iota, and -lambda isoforms in hGLCs and the translocation of PKCalpha subsequent to ATP treatment. In PKC-depleted cells the PKCalpha level was reduced, and no significant effect of ATP on hCG-stimulated cAMP production was observed. To our knowledge, this is the first demonstration of PKC isoforms in hGLCs and the involvement of activated PKC in mediating the antigonadotropic effect of extracellular ATP. Taken together, these results further support a role of this neurotransmitter in regulating human ovarian function.

Nitric oxide as a regulator in preimplantation embryo development and apoptosis.

OBJECTIVE: To investigate the mechanisms of nitric oxide (NO) in the development and apoptosis of preimplantation mouse embryos. DESIGN: Prospective, controlled study. SETTING: Medical college laboratory. SUBJECT(S): Two-cell embryos from outbred ICR mice. INTERVENTION(S): Hyperstimulation protocol, two-cell embryos were collected, then treated with or without an NO synthase inhibitor (L-NAME) or an NO donor (SNP) and combined with a cGMP analogue (8-Br-cGMP) or a selective inhibitor of NO-sensitive soluble guanylyl cyclase (ODQ). MAIN OUTCOME MEASURE(S): The development of ICR mouse embryo from two cells to blastocyst stages in vitro. RESULT(S): The development of blastocyst was inhibited by L-NAME in a concentration-dependent manner (0.1-10 microM) and 0.1 microM SNP reversed this effect (80.5% of control). Annexin-V/propidium iodide and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling techniques demonstrated that excessive NO (> or =10 microM) might induce apoptosis in the mouse embryos. 8-Br-cGMP reversed the inhibitory effect of L-NAME and rescued the embryo growth. ODQ inhibited the embryo development in a dose-responsive fashion (0.1--100 microM) but had no effect in the NO-induced embryo apoptosis. P53 and Bax were found to be up-regulated during the embryo fragmentation. CONCLUSION(S): These results indicate that the cGMP pathway might be involved in the NO-regulated embryonic development, but not in NO-induced apoptosis, for which P53/Bax pathway might be involved.

Adenosine triphosphate activates mitogen-activated protein kinase in human granulosa-luteal cells.

ATP has been shown to activate the phospholipase C/diacylglycerol/protein kinase C (PKC) pathway. However, little is known about the downstream signaling events. The present study was designed to examine the effect of ATP on activation of the mitogen-activated protein kinase (MAPK) signaling pathway and its physiological role in human granulosa-luteal cells. Western blot analysis, using a monoclonal antibody that detected the phosphorylated forms of extracellular signal-regulated kinase-1 and -2 (p42(mapk) and p44 (mapk), respectively), demonstrated that ATP activated MAPK in a dose- and time-dependent manner. Treatment of the cells with suramin (a P2 purinoceptor antagonist), neomycin (a phospholipase C inhibitor), staurosporin (a PKC inhibitor), or PD98059 (an MAPK/ERK kinase inhibitor) significantly attenuated the ATP-induced activation of MAPK. In contrast, ATP-induced MAPK activation was not significantly affected by pertussis toxin (a G(i) inhibitor). To examine the role of G(s) protein, the intracellular cAMP level was determined after treatment with ATP or hCG. No significant elevation of intracellular cAMP was noted after ATP treatment. To determine the role of MAPK in steroidogenesis, human granulosa-luteal cells were treated with ATP, hCG, or ATP plus hCG in the presence or absence of PD98059. RIA revealed that ATP alone did not significantly affect the basal progesterone concentration. However, hCG-induced progesterone production was reduced by ATP treatment. PD98059 reversed the inhibitory effect of ATP on hCG-induced progesterone production. To our knowledge, this is the first demonstration of ATP-induced activation of the MAPK signaling pathway in the human ovary. These results support the idea that the MAPK signaling pathway is involved in mediating ATP actions in the human ovary.

Role of mitogen-activated protein kinase in prostaglandin f(2alpha) action in human granulosa-luteal cells.

In the ovary it has been demonstrated that PGF(2alpha) activates the phospholipase C (PLC)/diacylglycerol/protein kinase C pathway. However, little is known about the downstream signaling events that mediate subsequent cellular responses such as steroidogenesis. The present study was designed to examine the effect of PGF(2alpha) on activation of the mitogen-activated protein kinase (MAPK) signaling pathway and its physiological role in human granulosa-luteal cells (hGLCs). Human GLCs, obtained from women undergoing in vitro fertilization-embryo transfer, were treated with increasing concentrations of PGF(2alpha) (10 nmol/L to 10 micromol/L) for 5 min. For time-course experiments, hGLCs were treated with 1 micromol/L PGF(2alpha) for 1, 5, 10, or 20 min. Western blot analysis, using a monoclonal antibody that detected the phosphorylated forms of extracellular signal-regulated kinases 1 and 2 (p42(mapk) and p44(mapk), respectively), demonstrated that PGF(2alpha) activated MAPK in hGLCs in a dose- and time-dependent manner. Treatment of the cells with neomycin (10 mmol/L; a PLC inhibitor), bisindolylmaleimide I (5 micromol/L; a PKC inhibitor), or PD98059 (50 micromol/L; a MEK inhibitor and a MAPK kinase inhibitor) significantly attenuated the PGF(2alpha)-induced activation of MAPK. In contrast, MAPK activation was not significantly affected by pertussis toxin (200 ng/mL; a G(i) inhibitor) pretreatment. To determine the role of MAPK in steroidogenesis, hGLCs were treated with PGF(2alpha) (1 micromol/L), hCG (1 IU/mL), or PGF(2alpha) plus hCG in the presence or absence of PD98059. Progesterone levels in the culture medium were examined by RIA. Treatment of hGLCs with PGF(2alpha) significantly inhibited hCG-induced progesterone production. The presence of the MEK inhibitor, PD98059, reversed the inhibitory effect of PGF(2alpha) on hCG-induced progesterone production. To our knowledge, it is the first demonstration of PGF(2alpha)-induced activation of the MAPK signaling pathway in the human ovary. These results indicated that PGF(2alpha) activated MAPK subsequent to PLC and PKC activation through pertussis toxin-insensitive G protein in hGLCs. Further, we demonstrated that PGF(2alpha)-induced MAPK activation is associated with modulation of progesterone production. These results support the idea that the MAPK signaling pathway is involved in mediating PGF(2alpha) actions in the human ovary.

Herniated blastomere following chemically assisted hatching may result in monozygotic twins.

OBJECTIVE: To explore a possible mechanism of the increasing incidence of monozygotic twins following assisted hatching of human embryos. DESIGN: Case report. SETTING: Clinical research center in a medical school teaching hospital. PATIENT: A 37-year-old infertile woman with repeated IVF failures. INTERVENTION(S): Assisted hatching of the day 3 embryos using acidic Tyrode's solution. MAIN OUTCOME MEASURE(S): The morphology of the zona-drilled embryos and the pregnancy outcome. RESULT(S): After assisted hatching, a herniated blastomere through an oversized opening in the zona pellucida was found in one embryo. The transfer of two zona-drilled embryos resulted in a triplet pregnancy. CONCLUSION(S): Large openings in the zona pellucida following chemically assisted hatching may cause premature hatching of the blastomeres and may be implicated in the occurrence of monozygotic twins.

Postoperative coma induced by hyponatremia after laparoscopy--a case report.

Hyponatremia is a common clinical entity which may occur during the course of many medical illnesses. However disastrous sequelae or even death may develop in young, generally healthy patients who receive simple elective surgery. Here we present a case of a 34-year-old female, without past history of cardiopulmonary or renal disease, after undergoing laparoscopic surgery developed mental status changes and lapsed into coma on the second postoperative day. She was found to have a serum sodium level of 110 mEq/L. After careful treatment and a protracted hospital stay, the patient recovered uneventfully. The pathophysiology of postoperative hyponatremia is discussed and attention is called to the special vulnerability of menstruant women who carry a much increased risk of mortality and morbidity associated with hyponatremia.