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Our purpose was to determine whether decreased follicle stimulating hormone (FSH) activity, either systemic or at the follicular level, is involved in impaired follicle growth associated with normogonadotrophic anovulation. To differentiate between the possible levels of disturbance, bioactive (BIO-FSH; using the in-vitro rat granulosa cell aromatase bioassay) and immunoreactive (IRMA-FSH) FSH serum concentrations of three groups of subjects were compared: (i) 172 normogonadotrophic anovulatory infertile women during baseline conditions, (ii) 22 clomi-phene-resistant polycystic ovary syndrome patients undergoing ovulation induction by exogenous gonadotrophins using a decremental dose regimen, and (iii) nine regularly cycling controls. BIO-FSH [13.2 (range 0.8–29.5) IU/1] and IRMA-FSH [4.4 (range 1.2–9.3) IU/1] concentrations in anovulatory women during baseline conditions were significantly lower than maximum concentrations reached during the follicular phase in controls [18.7 (13.2–23.4) and 6.4 (5.7–10.0) IU/1 respectively], but were not significantly different from initial concentrations in controls [10.4 (7.2–19.6) and 4.8 (2.8–8.2) IU/1 respectively]. Moreover, concentrations of IRMA-FSH and BIO-FSH were negatively correlated (r = −0.25, P = 0.01, and r = −0.24, P = 0.02 respectively) with the interval between last vaginal bleeding and blood sampling. Maximum concentrations of IRMA-FSH [7.6 (3.9–10.9) IU/1] during ovulation induction by gonadotrophins were not significantly different from [6.4 (5.7–10.0) IU/1] concentrations in controls, whereas maximum BIO-FSH concentrations [13.5 (8.7–17.4) versus 18.7 (13.2–23.4) IU/1] were significantly lower. Our findings suggest that (i) circulating FSH does not reach concentrations that are sufficient to induce normal follicle development in anovulatory women during base-line conditions, and (ii) the FSH threshold for ovarian stimulation of this patient group is not different from normal [ABSTRACT FROM PUBLISHER]

This case report describes the first established pregnancy and birth after induction of ovulation with recombinant human follicle-stimulating hormone (FSH) in a woman suffering from chronic clomiphene-resistant anovulation due to polycystic ovary syndrome (elevated serum luteinizing hormone and testosterone concentrations together with polycystic ovaries). Starting on day 3 of a progestagen withdrawal bleeding, 75 IU of rFSH was administered i.m. daily until a single preovulatory follicle was seen upon transvaginal ultrasound examination at day 13. Ovulation was induced by a single i.m. administration of 10,000 IU of human chorionic gonadotrophin, after which a viable singleton pregnancy was revealed at a gestational age of 6 weeks. The course of pregnancy and labour was uneventful and no abnormalities were found upon a paediatric examination. [ABSTRACT FROM AUTHOR]

Cervical mucus may cover the embryo transfer catheter during passage of the cervical canal, interfering with the correct placement of the embryo(s) into the uterine cavity. The effect of removal of cervical mucus prior to embryo transfer in IVF/ intracytoplasmic sperm injection (ICSI) on live birth rate was studied. The study was set up as a single blind randomized controlled trial. Couples undergoing IVF/ICSI were randomly allocated to either removal of cervical mucus prior to embryo transfer, or a mock procedure. Randomization was done with stratification for age, cycle number and method of treatment. Primary outcome was live birth rate. A total of 317 couples were included and underwent 428 cycles, of which the outcome of 3 cycles was unknown. Baseline characteristics of both groups were comparable. Live birth occurred in 52 of 220 (24%) cycles in the treatment group and 42 of 205 (21%) cycles in the control group (risk difference 3%, 95% confidence interval -5-11%). It is unlikely that removal of cervical mucus prior to embryo transfer has a significant effect on live birth rate. A small effect, however, cannot be excluded. [ABSTRACT FROM AUTHOR]

The Chlamydia antibody titre (CAT) is a test used to identify subfertile couples at increased risk for tubal pathology. The usefulness of the routine performance of CAT was evaluated in a multicentre prospective cohort study, in women without regular ovulation. Consecutive couples presenting with subfertility due to an irregular menstrual cycle or amenorrhoea were included. A total of 711 women were studied, all of whom underwent CAT. Tubal status was verified in 190 of these women. Two-sided tubal pathology was found in 5% of these women, and one-sided occlusion in 10%. Of all the women in the study group, 33 (4.6%) had an abnormal CAT, of which 21 underwent further tubal testing. Tubal pathology was found in two (10%) of these 21 patients. The sensitivity and specificity of CAT were respectively 20% and 89%. Correction for verification bias increased the specificity to 96% with a drop of the sensitivity to 9%. In subfertile couples with anovulation, the performance of CAT is not useful. It is proposed that testing for tubal disease in these women is delayed until treatment with elomiphene citrate has failed. [ABSTRACT FROM AUTHOR]

Objective: To predict instrumental vaginal delivery or caesarean section for suspected fetal distress or failure to progress., Design: Secondary analysis of a randomised trial., Setting: Three academic and six non-academic teaching hospitals in the Netherlands., Population: 5667 labouring women with a singleton term pregnancy in cephalic presentation., Methods: We developed multinomial prediction models to assess the risk of operative delivery using both antepartum (model 1) and antepartum plus intrapartum characteristics (model 2). The models were validated by bootstrapping techniques and adjusted for overfitting. Predictive performance was assessed by calibration and discrimination (area under the receiver operating characteristic), and easy-to-use nomograms were developed., Main Outcome Measures: Incidence of instrumental vaginal delivery or caesarean section for fetal distress or failure to progress with respect to a spontaneous vaginal delivery (reference)., Results:   375 (6.6%) and 212 (3.6%) women had an instrumental vaginal delivery or caesarean section due to fetal distress, and 433 (7.6%) and 571 (10.1%) due to failure to progress, respectively. Predictors were age, parity, previous caesarean section, diabetes, gestational age, gender, estimated birthweight (model 1) and induction of labour, oxytocin augmentation, intrapartum fever, prolonged rupture of membranes, meconium stained amniotic fluid, epidural anaesthesia, and use of ST-analysis (model 2). Both models showed excellent calibration and the receiver operating characteristics areas were 0.70-0.78 and 0.73-0.81, respectively., Conclusion:   In Dutch women with a singleton term pregnancy in cephalic presentation, antepartum and intrapartum characteristics can assist in the prediction of the need for an instrumental vaginal delivery or caesarean section for fetal distress or failure to progress., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

Background: Guidelines recommend diagnostic laparoscopy in subfertile women with known co-morbidities in their medical history. Aggregated evidence underpinning these recommendations is, however, currently lacking., Objective: The objective of this study was to perform a systematic review and meta-analysis of the available evidence on the association between items reported during medical history taking and tuboperitoneal pathology., Search Strategy: MEDLINE (from 1966 to May 2007), EMBASE (from 1960 to January 2007) and bibliographies of retrieved primary articles., Selection Criteria: All relevant studies that compared medical history with the presence or absence of tubal pathology., Data Collection and Analysis: Studies comparing medical history with the presence or absence of tubal pathology were included. A diagnosis of tubal pathology had to be made by hysterosalpingography, laparoscopy or a combination of both. In the absence of invasive tubal testing, tuboperitoneal pathology was considered to be absent in case of intrauterine pregnancy. Homogeneity between studies was assessed, and the association between medical history and tubal pathology was expressed as a common odds ratio with a 95% CI. No language restriction was applied., Main Results: We included 32 studies. In cohort studies, strong associations were found for a history of complicated appendicitis (OR 7.2, 95% CI 2.2-22.8), pelvic surgery (OR 3.6, 95% CI 1.4-9.0) and pelvic inflammatory disease (PID) (OR 3.2, 95% CI 1.6-6.6), and in case-control studies, for a history of complicated appendicitis (OR 3.3, 95% CI 1.8-6.3), PID (OR 5.5, 95% CI 2.7-11.0), ectopic pregnancy (OR 16.0, 95% CI 12.5-20.4), endometriosis (OR 5.9, 95% CI 3.2-10.8) and sexually transmitted disease (OR 11.9, 95% CI 4.3-33.3)., Author's Conclusions: Subfertile women reporting a history of PID, complicated appendicitis, pelvic surgery, ectopic pregnancy and endometriosis are at increased risk of having tuboperitoneal pathology. In these women, diagnostic laparoscopy should be offered early in the fertility work-up.

Background: Prediction models for spontaneous pregnancy may be useful tools to select subfertile couples that have good fertility prospects and should therefore be counselled for expectant management. We assessed the accuracy of a recently published prediction model for spontaneous pregnancy in a large prospective validation study., Methods: In 38 centres, we studied a consecutive cohort of subfertile couples, referred for an infertility work-up. Patients had a regular menstrual cycle, patent tubes and a total motile sperm count (TMC) >3 x 10(6). After the infertility work-up had been completed, we used a prediction model to calculate the chance of a spontaneous ongoing pregnancy (www.freya.nl/probability.php). The primary end-point was time until the occurrence of a spontaneous ongoing pregnancy within 1 year. The performance of the pregnancy prediction model was assessed with calibration, which is the comparison of predicted and observed ongoing pregnancy rates for groups of patients and discrimination., Results: We included 3021 couples of whom 543 (18%) had a spontaneous ongoing pregnancy, 57 (2%) a non-successful pregnancy, 1316 (44%) started treatment, 825 (27%) neither started treatment nor became pregnant and 280 (9%) were lost to follow-up. Calibration of the prediction model was almost perfect. In the 977 couples (32%) with a calculated probability between 30 and 40%, the observed cumulative pregnancy rate at 12 months was 30%, and in 611 couples (20%) with a probability of >or=40%, this was 46%. The discriminative capacity was similar to the one in which the model was developed (c-statistic 0.59)., Conclusions: As the chance of a spontaneous ongoing pregnancy among subfertile couples can be accurately calculated, this prediction model can be used as an essential tool for clinical decision-making and in counselling patients. The use of the prediction model may help to prevent unnecessary treatment.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulation in women. Previous studies suggest that the pathogenesis of PCOS may involve interrelated abnormalities of the insulin-like growth factor (IGF) and ovarian steroidogenesis systems. We investigated this hypothesis in fasting serum samples from 140 women with PCOS (age, 27.4 +/- 0.4 yr; body mass index, 26.3 +/- 0.5 kg/m2; mean +/- SEM). IGF-related parameters were also studied in a group of normoovulatory women (n = 26; age, 26 +/- 4 yr; body mass index, 23.6 +/- 4.3 kg/m2). For the PCOS group, the mean testosterone (T) level was 2.5 +/- 0.1 nmol/L, and it was significantly correlated with LH (r = 0.41; P < 10(-6)), estrone (r = 0.33; P = 0.016), estradiol (r = 0.18; P = 0.04), and androstenedione (AD; P < 10(-6)), but not with dehydroepiandrosterone sulfate (P = 0.71), a marker of adrenal steroidogenesis. T and AD were also related to total ovarian follicle number and ovarian size, as previously found with normoovulatory women (1). There were no differences between the PCOS subjects and the normoovulatory group for total IGF-I, IGF-II, or IGF-binding protein-3 (IGFBP-3). However, IGFBP-1 levels were significantly decreased in the PCOS group (1.0 +/- 0.2 vs. 7.3 +/- 1.1 ng/mL; P < 0.001) and were inversely correlated with serum insulin levels (r = -0.50; P < 10(-8)). Serum levels of free IGF-I (fIGF-I) were elevated (5.9 +/- 0.3 vs. 2.7 +/- 0.3 ng/mL; P < 0.001) in inverse relation with IGFBP-1 (r = -0.31; P = 0.046). Serum fIGF-I levels were related to total follicle number (r = - 0.35; P < 10(-4)) and to the ratio of sex hormone-binding globulin to T (r = -0.23; P = 0.009). However, these relationships were not independent of other variables. Despite the more than 2-fold elevation in fIGF-I levels, significant relationships between fIGF-I and markers of ovarian steroidogenesis (T, AD, estradiol, and estrone) could not be demonstrated. In conclusion, although we confirmed correlations between LH and hyperandrogenemia and have found abnormalities in the IGF system in a large cohort of PCOS subjects, a direct relationship between hyperandrogenism and the IGF system could not be shown. Previous studies suggest that elevated LH and hyperinsulinemia lead to excess ovarian androgen synthesis in PCOS and that the intraovarian IGF system is important for normal follicle development and may be important in the arrested state of follicle development in PCOS. However, the data presented in this cross-sectional study suggest that insulin-related changes in circulating IGFBP-1 and subsequent elevation of fIGF-I reflect insulin resistance and have little enhancing effects on ovarian steroidogenesis in this disorder.

Objective: To determine the probability of pregnancy after a finished extrauterine pregnancy (EUP) and the length of time in between., Design: Prospective multicentric cohort study., Method: Of all patients with an EUP between May 1990 and October 1993, data were collected using a questionnaire from surgeons in five university hospitals and 30 general training and non-training hospitals. During the subsequent 3 years, the patients semi-annually reported on their pregnancy or wish to become pregnant using reply cards., Results: A total of 665 patients with an EUP were reported their mean age was 30.7 years (SD: 4.9). There were 341 patients who during the follow-up desired pregnancy, did not start an IVF procedure and supplied complete follow-up data 207 of them (61%) became pregnant after a median interval of 12 months. Age above 35, previous fertility problems, a Chlamydia antibody titre > or = 1:64 and adnexitis in the anamnesis were correlated with a longer interval until a subsequent pregnancy. The nature of the treatment (laparotomy versus laparoscopy, conservative versus radical and surgical versus pharmaceutical) did not affect the duration of the interval. If the contralateral tube was judged to be abnormal by the operator, pregnancy was still possible, but the occurrence of the pregnancy was delayed., Conclusion: The probability of pregnancy after an earlier EUP averages 61%; the interval until the next pregnancy, if any, depends mostly on factors that cannot be influenced at the time of the diagnosis of EUP.

Objective: To determine insulin-like growth factor (IGF)-I and IGF-II levels, IGF binding protein (IGFBP) profile, and IGFBP-4 protease activity in androgen-dominant follicular fluid (FF) from female-to-male trans-sexuals and to compare with those in follicles from normocycling women., Design: Follicular fluid samples were obtained from four female-to-male trans-sexuals and 15 women with normo-ovulatory cycles at the Dijkzigt Academic Hospital. Western ligand blot analysis and protease assays were used to determine IGFBP profile, and immunoradiometric assays were used to detect IGF levels., Setting: The study was performed in two academic medical centers., Patient(s): Female-to-male trans-sexuals and women with normo-ovulatory cycles., Interventions: None., Main Outcome Measure(s): Determination of IGF levels and IGFBP profile., Result(s): Insulin-like growth factor I levels in FF from female-to-male trans-sexuals were not significantly different compared with levels in androgen-dominant FF and estrogen-dominant FF. Significantly lower levels of IGF-II were observed in FF from female-to-male trans-sexuals than in estrogen-dominant FF, whereas IGF-II levels in FF from female-to-male trans-sexuals were not significantly different than those in androgen-dominant FF. Similar IGFBP profiles from FF from female-to-male trans-sexuals and androgen-dominant FF were noted, with markedly elevated levels of the 31- and 24-kd IGFBPs and a 28-kd IGFBP, compared with estrogen-dominant FF. An IGFBP-4-specific metalloserine protease that is active in estrogen-dominant FF likewise was undetected in FF from female-to-male trans-sexuals., Conclusion(s): Follicles developing under the influence of exogenous androgens in ovaries in female-to-male trans-sexuals appear to be similar to androgen-dominant follicles in normo-ovulatory women with regard to IGF-I and IGF-II levels, IGFBP profile, and the absence of IGFBP-4 protease activity.

IGFs function as co-gonadotropins in the ovary, facilitating steroidogenesis and follicle growth. IGFBP-1 to -5 are expressed in human ovary and mostly inhibit IGF action in in vitro ovarian cell culture systems. In the clinical disorder of polycystic ovarian syndrome (PCOS), which is characterized by hyperandrogenemia, polycystic ovaries and anovulation, follicles have a higher androgen: estradiol (A : E2) content and growth is arrested at the small antral stage. In the PCOS follicle, follicle stimulating hormone (FSH) and IGF levels are in the physiologic range, and even in the face of abundant androstenedione (AD) substrate, aromatase activity and E2 production are low. When PCOS granulosa are removed from their ovarian environment, they respond normally or hyperrespond to FSH. It has been postulated that an inhibitor of IGF's synergistic actions with FSH on aromatase activity may be one (or more) of the IGFBPs, which contributes to the arrested state of follicular development commonly observed in this disorder. High levels of IGFBP-2 and IGFBP-4 are present in follicular fluid (FF) from androgen-dominant follicles (FFa) from normally cycling women and in women with PCOS. This is in marked contrast to the near absence of these IGFBPs in estrogen-dominant FF (FFe), determined by Western ligand blotting. Regulation of granulosa-derived IGFBPs is effected by gonadotropins and insulin-like peptides. In addition, an IGFBP-4 metallo-serine protease is present in FFe, but not in FFa in ovaries from normally cycling women and those with PCOS, although the IGFBP-4 protease is present in PCOS follicles hyperstimulated for in vitro fertilization. Recent studies demonstrate that IGF-II in FFe is higher than in FFa' whereas IGF-I, IGFBP-3 and IGFBP-1 levels do not differ, underscoring the importance of local IGF-II production by the granulosa and the importance of IGFBP-4 and IGFBP-2 in regulation of IGF-II action within the follicle during its developmental pathway as an E2- or A-dominant follicle. In the androgen-treated female-to-male transsexual (TSX) model for PCOS, IGF-I, IGF-II, IGFBP-3 and IGFBP-1 levels do not differ.

Objective: Assessment of cervical dynamics during the first stage of labor by a combination of ultrasound cervimetry and intrauterine tocography., Methods: Sixty-two parturients were divided into four groups: nulliparous women in spontaneous (n = 9) or oxytocin-induced labor (n = 26), parous women in spontaneous (n = 11) or oxytocin-induced labor (n = 16). Intrauterine pressure and cervical dilatation were continuously recorded and assessed by off-line computer analysis., Results: All women with spontaneous labor showed cervical responses to uterine contractions at the beginning of the recording. The first cervical response to a uterine contraction occurred at a significantly smaller dilatation in parous than in nulliparous women with induced labor (2.9 and 3.6 cm, respectively). Also, acceleration of cervical dilatation occurred at less dilatation in parous than in nulliparous women (3.4 cm and 4.8 cm, respectively), and myometrial work per cm of cervical dilatation was less in parous than in nulliparous parturients., Conclusions: The results indicate significant differences between cervical dilatation patterns in nulliparous and parous women, which may be due to structural cervical changes caused by labor and parturition. The labor patterns found were different from those originally described by Friedman (Friedman EA. Graphic analysis of labor. Am J Obstet Gynecol 1954; 68: 1568-1575), as no deceleration phases were detected. Ultrasound cervimetry is a valuable technique for the study of cervical dynamics during labor.