Cesarean scar niche, fertility and uterine rupture during labor - A retrospective study.

OBJECTIVES: To determine how does a uterine niche diagnosed prior to conception, affects future fertility and obstetrical outcomes, in a group of patients with secondary infertility undergoing fertility treatments. STUDY DESIGN: A retrospective case-control study was performed, recruiting patients after cesarean delivery, before fertility treatment. Using stored ultrasound photos and video loops, we determined niche's sonographic parameters during the preconception period and retrieved the fertility and obstetrical outcomes thereafter. RESULTS: 104 patients met the inclusion criteria, and 86 were available for analysis. 56 (65%) had uterine niches larger than 2 mm in depth, and 30 (34%) had a uterine scar of 2 mm or less. Demographic characteristics were not different between groups. No statistically significant differences were observed regarding rates of implantation and clinical pregnancy between the groups. There were four cases of cesarean scar rupture during failed trial of labor (TOLAC), all of which were in the group with larger than 2 mm niche (33% of all TOLAC cases in the respected group). CONCLUSIONS: While it appears that pre-conception presence of uterine niches larger than 2 mm in depth does not adversely affect future fertility, these niches might serve as a risk factor for future uterine rupture during TOLAC.

MYO10 promotes transzonal projection-dependent germ line-somatic contact during mammalian folliculogenesis†.

Granulosa cells of growing ovarian follicles elaborate filopodia-like structures termed transzonal projections (TZPs) that supply the enclosed oocyte with factors essential for its development. Little is known, however, of the mechanisms underlying the generation of TZPs. We show in mouse and human that filopodia, defined by an actin backbone, emerge from granulosa cells in early stage primary follicles and that actin-rich TZPs become detectable as soon as a space corresponding to the zona pellucida appears. mRNA encoding Myosin10 (MYO10), a motor protein that accumulates at the base and tips of filopodia and has been implicated in their initiation and elongation, is present in granulosa cells and oocytes of growing follicles. MYO10 protein accumulates in foci located mainly between the oocyte and innermost layer of granulosa cells, where it colocalizes with actin. In both mouse and human, the number of MYO10 foci increases as oocytes grow, corresponding to the increase in the number of actin-TZPs. RNAi-mediated depletion of MYO10 in cultured mouse granulosa cell-oocyte complexes is associated with a 52% reduction in the number of MYO10 foci and a 28% reduction in the number of actin-TZPs. Moreover, incubation of cumulus-oocyte complexes in the presence of epidermal growth factor, which triggers a 93% reduction in the number of actin-TZPs, is associated with a 55% reduction in the number of MYO10 foci. These results suggest that granulosa cells possess an ability to elaborate filopodia, which when directed toward the oocyte become actin-TZPs, and that MYO10 increases the efficiency of formation or maintenance of actin-TZPs.

When to do intracytoplasmic sperm injection: a prospective comparison.

PURPOSE: The purpose of the study was to assess the fertilization rate and embryo development in sibling human oocytes after split insemination in patients with and without isolated teratozoospermia. METHODS: A prospective cohort study at a university affiliated reproduction center was performed. Hundred and three patients during the time periods 01-2013 to 12-2015 had split insemination ordered for their first IVF cycle. The primary outcome measured was fertilization rate. Secondary outcomes were the number and quality of embryos. RESULTS: Mature oocytes at the time of collection were assigned as follows: 558 to IVF and 556 to ICSI. An additional 48 immature oocytes matured while awaiting spontaneous fertilization with IVF for a total of 606 in that group. The study group of normal strict sperm morphology ≤ 4 included 61 patients, and the control group included 42 patients with normal strict sperm morphology > 4. ICSI was statistically favored over IVF only in cases with normal strict sperm morphology ≤ 4%. There was a higher fertilization rate in ICSI compared to IVF (74.4% vs. 38%, p < 0.0001), a higher number of day 2 (4 ± 3.4 vs. 2.4 ± 2.7, p < 0.0001), day 3 (4 ± 3.4 vs. 2.2 ± 2.7, p < 0.0001) and day 5 embryos (2.2 ± 2.6 vs. 1.2 ± 2, p = 0.001), and they were of better quality; however, it did not reach significance (p = 0.062). A similar advantage for ICSI was seen in a subgroup of unexplained infertility with normal strict sperm morphology > 4%. CONCLUSIONS: In conclusion, in couples with normal strict sperm morphology ≤ 4%, there is an advantage of ICSI over IVF in terms of fertilization rate, quantity and quality of cleavage stage embryos and blastocysts. Based on the results, ICSI seems reasonable as a first-line treatment in patients with normal strict sperm morphology ≤ 4%, as well as in patients with unexplained infertility.

Decreased pregnancy and live birth rates after vitrification of in vitro matured oocytes.

PURPOSE: To assess effects on fertilization rate, embryo quality, pregnancy, and live birth rates of vitrification and warming of oocytes that matured in vitro (vIVM) compared to fresh in vitro maturation (fIVM) cycles. METHODS: A retrospective cohort study conducted at a university hospital-affiliated IVF unit. Fifty-six cycles of vIVM cycles and 263 fIVM in women diagnosed with polycystic ovarian syndrome (PCOS) ovaries were included in the analysis. The study group included PCOS patients who failed ovulation induction with intrauterine insemination and were offered IVM cycle followed by oocyte vitrification and warming. The embryological aspects and clinical outcomes were compared to those of controls undergoing fresh IVM cycles during the same period. The main outcome measure was live birth rate. RESULTS: One thousand seventy oocytes were collected from 56 patients and underwent vitrification and warming. In the control group, 4781 oocytes were collected from 219 patients who had undergone a fresh IVM cycle. Oocyte maturation rates were similar between the groups (mean ± SD: 0.7 ± 0.2 vs. 0.6 ± 0.2, for vIVM and fIVM, respectively). Survival rate after warming was 59.8%. Fertilization and embryo cleavage rates per oocyte were significantly lower in the vIVM group. Clinical pregnancy (10.7 vs. 36.1%) and live birth rates (8.9 vs. 25.9%) per cycle were significantly lower in the vIVM group than those in the fIVM group (P = 0.005 and P < 0.001, respectively). Five healthy babies were born in the vIVM group. CONCLUSIONS: The reproductive potential of vitrified IVM oocytes is impaired. This injury likely occurs through vitrification and warming.

Conservative Surgery for Adenomyosis and Results: A Systematic Review.

The traditional treatment for women with symptomatic adenomyosis is hysterectomy. However, reproductive-aged women should be managed with less invasive treatments including medical treatment. For patients who are refractory or unsuitable to long-term medical treatment or those with focal adenomyoma, conservative surgeries could be offered. The objective of our study was to review available conservative surgeries for the treatment of adenomyosis, their complications, and the rates of success and recurrence. In this systematic review we evaluated 27 studies; 10 prospective and 17 retrospective studies including a total of 1398 patients. The results showed that excision of adenomyosis is effective for symptom control such as menorrhagia and dysmenorrhea and most probably for adenomyosis-related infertility. For preserving fertility and relieving symptoms, medical treatment is usually the first choice, whereas excisional surgery could be performed for refractory adenomyosis. The results show that over three-fourths of women will experience symptom relief after conservative surgery. The pregnancy rates after conservative surgical treatment vary widely. However, three-fourths of them conceived after surgery with or without adjuvant medical treatment. Depending on the duration of follow-up, recurrence rates differ from no recurrence to almost one-half of patients. Conservative surgery for adenomyosis improves pelvic pain, abnormal uterine bleeding, and possibly fertility. The best method of surgery is yet to be seen.

Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis.

OBJECTIVE: To systematically review and summarize the existing evidence related to the effect of adenomyosis on fertility and on in vitro fertilization (IVF) clinical outcomes, and to explore the effects of surgical or medical treatments. DESIGN: Meta-analysis. SETTING: Not applicable. PATIENT(S): An electronic-based search was performed with the use of the following databases: Pubmed, Embase, Ovid Medline, Cochrane Central Register of Controlled Trials, and Google Scholar, identifying all related articles up to November 2016. We included 11 comparative studies that evaluated the clinical outcomes of IVF treatments in women with (519 patients) and without (1,535 patients) adenomyosis diagnosed with the use of magnetic resonance imaging or transvaginal ultrasound. We also separately evaluated four articles comparing fertility outcomes in two groups of infertile adenomyotic patients untreated and treated surgically or medically with the use of GnRH agonist (GnRHa). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcome: clinical pregnancy rate after IVF. SECONDARY OUTCOMES: rates of implantation, ongoing pregnancy, live birth, miscarriage, and ectopic pregnancy. The summary measures were expressed as odds ratio (OR) and 95% confidence interval (CI). RESULT(S): The rates of implantation, clinical pregnancy per cycle, clinical pregnancy per embryo transfer, ongoing pregnancy, and live birth among women with adenomyosis were significantly lower than in those without adenomyosis. The miscarriage rate in women with adenomyosis was higher than in those without adenomyosis. It appears that surgical treatment or treatment withf GnRHa increases the spontaneous pregnancy rate in women with adenomyosis. CONCLUSION(S): Adenomyosis has a detrimental effect on IVF clinical outcomes. Pretreatment with the use of long-term GnRHa or long protocol could be beneficial.

The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age.

STUDY QUESTION: Does ICSI improve reproductive outcomes compared with conventional IVF when used for non-male factor infertility in women aged 40 years and over? SUMMARY ANSWER: There is no advantage of ICSI over conventional IVF in women aged 40 years and over when used for non-male factor infertility. WHAT IS KNOWN ALREADY: The use of ICSI has increased dramatically in recent years and is being applied for indications other than male factor infertility. Currently, ICSI is used in 65% of IVF cycles in Europe and in 76% of cycles in the USA. Despite its increase use, there is no clear evidence of a benefit in using ICSI over conventional IVF. Older women undergoing infertility treatments are at an increased risk of having diminished ovarian reserve and lower oocyte quality, which could make ICSI the preferred insemination method in this group. However, studies that have examined the benefits of ICSI in this age group are lacking. STUDY DESIGN, SIZE, DURATION: A retrospective, single center study included women, aged 40-43 years, who underwent IVF treatments for non-male factor infertility between January 2012 until June 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 745 women were included in the study. Of these, 490 women underwent ICSI and 255 women underwent conventional IVF. In order to be included in the study, women had to be at least 40 years of age at the beginning of ovarian stimulation and their male partner had to have normal sperm parameters according to World Health Organisation (WHO) fifth edition. Exclusion criteria included: more than three previous IVF cycles, a history of fertilization failure or low fertilization (<50%), the use of donor or frozen oocytes and the use of donor or frozen sperm samples. The primary outcome was the live birth rate. Secondary outcomes included fertilization rates, fertilization failure and embryo quality. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics were similar between the two groups, except for the number of previous IVF cycles, which was higher in the ICSI group (1.0 vs. 0.6, P = 0.0001). Despite similar numbers of oocytes retrieved (7.2 vs. 6.5), when examining oocytes maturity (performed 2 h after oocyte retrieval in the ICSI group and after 18 h in the conventional IVF group), the conventional IVF group had a higher number of Metaphase II (MII) oocytes (6.1 vs. 4.7, P < 0.0001). The conventional IVF group also had higher numbers of zygotes formed (4.48 vs. 3.66, P = 0.001), more cycles with embryos transferred at the blastocyst stage (36 vs. 26%, P = 0.005) and more cycles where embryos were available for cryopreservation (26.4 vs. 19.7%, P = 0.048), compared with the ICSI group. The fertilization rates (64 vs. 67%) and fertilization failure (9.0 vs. 9.7%) were similar. After logistic regression analysis controlling for confounders, the live birth rates were similar between the groups (11.9 vs. 9.6%). Subgroup analyses of women undergoing their first IVF cycle and women with ≤3 oocytes retrieved did not show an advantage of ICSI over conventional IVF. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of this study was a major limitation. The ICSI group had a higher number of previous IVF cycles, which could mean that ICSI was performed in poorer prognosis patients. Moreover, although this study is one of the largest studies to examine the question of whether ICSI is of value for older women with non-male factor infertility, based on a post hoc power analysis, it was still underpowered to detect differences in live birth rates, which can limit the conclusions of the study. Prospective studies are needed to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: The decision regarding performing ICSI should be based on sperm parameters and previous history. The use of ICSI for the sole indication of advanced maternal age shows no benefit over conventional IVF. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

The mutual effect of pregestational body mass index, maternal hyperglycemia and gestational weight gain on adverse pregnancy outcomes.

OBJECTIVE: To investigate the mutual effect of obesity, gestational diabetes (GDM) and gestational weight gain (GWG) on adverse pregnancy outcomes. METHODS: Charts of patients who delivered in our hospital between June 2001 and June 2006 singleton, live births >24 weeks gestation were reviewed. Univariate and multivariate logistic regression were used to assess pregnancy outcomes defined as large for gestational age (LGA), primary cesarean section (PCS) and a composite outcome of LGA and/or PCS. RESULTS: A total of 8595 women were included. Frequency of composite outcome increased with increasing body mass index (BMI), increasing hyperglycemia and above-recommended GWG. In the multivariate logistic regression analysis compared to women with normal BMI, odds ratio (OR) for composite outcome was 1.23 (95% confidence interval [CI] 1.06-1.44) in overweight women, OR = 1.86 (1.51-2.31) in obese women and in severe obesity OR = 2.97 (2.15-4.11). Compared to normoglycemic women, odds for composite outcome in women with abnormal glucose challenge test OR = 1.46 (1.20-1.79), impaired glucose tolerance OR = 1.65 (1.14-2.4) and GDM OR = 1.56 (1.16-2.10). Women with GWG above recommended had OR = 1.58, (1.37-1.81) for composite outcome. CONCLUSIONS: Higher pregestational BMI, maternal hyperglycemia and above-recommended GWG independently contribute to adverse pregnancy outcomes. Furthermore, there is mutual effect between these three factors and adverse outcomes. Appropriate pregestational weight and adequate GWG might reduce risk of adverse pregnancy outcomes.

Oxidative markers in cryopreservation medium from frozen-thawed embryos: a possible tool for improved embryo selection in in vitro fertilization?

PURPOSE: The present study evaluated the association between oxidative parameters in embryo cryopreservation medium and laboratory and clinical outcomes. METHODS: This prospective laboratory study was conducted in an IVF unit in a university-affiliated hospital with 91 IVF patients undergoing a frozen-thawed embryo transfer cycle. Following thawing, 50 µL of embryo cryopreservation medium was retrieved from each cryotube and tested by the thermochemiluminescence (TCL) assay. TCL amplitudes after 50 (H1), 150 (H2), and 280 s (H3) were recorded in counts per second (CPS) and the TCL ratio determined for comparison with implantation and pregnancy rates. RESULTS: A total of 194 embryos were transferred in 85 frozen-thaw cycles. Twenty-one pregnancies (24.7 %) occurred. Implantation and overall and clinical pregnancy rates were higher when the median TCL H1 amplitude was <32 CPS compared to ≥32 CPS (14.6 vs. 5.3 %, 37.5 vs. 17 %, 28.1 vs. 9.4 %, respectively). No pregnancies occurred when the H1 amplitude was ≥40 CPS. Logistic regression multivariate analysis found that only the median TCL H1 amplitude was associated with the occurrence of pregnancy (OR = 2.93, 95 % CI 1.065-8.08). The TCL ratio inversely correlated with the duration of embryo cryopreservation (r = -0.37). CONCLUSIONS: The results indicate that thawed embryos may express oxidative processes in the cryopreservation medium, and higher oxidative levels are associated with lower implantation rates. These findings may aid in the improved selection of frozen-thawed embryos for IVF.

The prognostic significance of hematological parameters in women with uterine serous papillary carcinoma (USPC).

OBJECTIVES: Preoperative hematologic parameters: thrombocytosis, leukocytosis and anemia have been demonstrated to be independent poor prognostic factors in ovarian and endometrial cancers. However, little is known about their relation to uterine serous papillary carcinoma (USPC). We evaluated several preoperative hematologic parameters and their association with clinicopathologic features, disease progression and overall survival in USPC patients. STUDY DESIGN: This was a retrospective cohort study reviewing charts of all patients with a histologic pure USPC at two gynecologic oncology centers from January 2000 through July 2012. All patients had comprehensive hematologic tests prior to primary surgical treatment and were exposed to the same adjuvant treatment protocol. RESULTS: The study included 56 patients, mean age at diagnosis 69.4±15. Six (11%) had platelet count above 400000 10(6)/L, of them four (66%) were dead at the end of follow up (HR=1.4, p=0.48; CI 95% 0.5-4.3). The mean hemoglobin level was 12.3g/dl, fibrinogen 437.5mg/dL and lymphocytes 2013/µL. None of these parameters was significantly associated with 5 year survival. Leukocyte and neutrophil levels were adversely associated with survival. Of 15 patients with leukocytosis >10000/µL, 67% were dead at the end of follow up (HR=3.98, p=0.003; CI 95% 1.6-9.8). Of the 27 with neutrophils above 65%, 14 (52%) were dead at the end of follow up (HR=3.1; p=0.015; CI 95% 1.2-7.8). CONCLUSIONS: In patients with USPC, leukocytosis and neutrophilia are associated with aggressive tumor biology, and may predict a lower 5 year survival.

Clinical and Pathological Characteristics of Incidental Diagnostic Early Occult Malignancy After Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers.

OBJECTIVE: Carriers of familial BRCA mutations are at high risk of early development of ovarian tubal or peritoneal cancers. The definite preventative treatment for these cases is early, risk-reducing, bilateral salpingo-oophorectomy (BSO). The aims of the study were to describe the incidence and source of early occult malignancy after risk-reducing salpingo-oophorectomy in carriers of Ashkenazi Jewish BRCA mutations and to characterize the clinical and pathological features of this unique population. METHODS: Data were collected retrospectively regarding women who underwent BSO in our gynecologic oncology unit from January 2002 through July 2012, after a positive test for a BRCA1 or BRCA2 mutation. RESULTS: The following 92 cases of BRCA mutations were included: 53 BRCA1, 37 BRCA2, and 2 with both mutations. After risk-reducing salpingo-oophorectomy, 5 (5.4%) of the patients were found to have early occult adnexal malignancy upon pathology study. All 5 had the BRCA1 185 del-AG mutation. Three of the 5 malignancies originated from the ovaries and 2 in the fallopian tubes with no involvement of the ovaries. CONCLUSIONS: A 5.4% incidence of early occult malignancy in adnexal pathology of BSO was found in carriers of Ashkenazi Jewish BRCA mutations. Two cases with malignant origins within the fallopian tube, while sparing the ovaries in their entirety, support the fallopian tubes as the originating organ for some ovarian or peritoneal malignancies in BRCA mutation carriers.

Vaginal adhesions after transvaginal pelvic reconstructive surgeries: prevalence and clinical implications.

INTRODUCTION AND HYPOTHESIS: Our aim was to assess the prevalence of vaginal adhesions after transvaginal pelvic reconstructive surgeries and evaluate relevant risk factors and impact on surgical outcome and sexual function. METHODS: This was a retrospective study examining medical records of all patients undergoing transvaginal pelvic reconstructive surgeries for pelvic organ prolapse (POP) at our institution between January 2006 and December 2007. RESULTS: One hundred and ninety -nine women were included in the study, of whom 165 had a comprehensive pre- and postoperative follow-up assessment and were available for final analysis. Vaginal adhesions were reported in 18 (10.9%) women during the first follow-up visit 36 ± 34 days postoperatively. Adhesions were reported to be successfully separated manually in all cases during pelvic examination. Patients with or without vaginal adhesions showed no statistically significant differences in demographic, obstetric, or clinical characteristics or in severity of prolapse. No statistically significant correlation was found between any specific surgical procedure and the risk of developing vaginal adhesions. Rates of prolapse recurrence, postoperative vaginal narrowing and dyspareunia were not significantly different between groups. CONCLUSIONS: Vaginal adhesion formation is a relatively common complication after transvaginal pelvic reconstructive surgeries unrelated to preoperative degree of prolapse or to the type of surgery. If adhesions are separated manually at an early stage, surgical outcome and sexual function do not seem to be adversely affected.

Effects of treatment of ectopic pregnancy with methotrexate or salpingectomy in the subsequent IVF cycle.

Ectopic pregnancy is a known risk for patients treated with IVF. The objective of this study was to evaluate the effect of methotrexate (MTX) and laparoscopic salpingectomy as treatments of ectopic pregnancy on ovarian response during IVF cycles. Data of all women treated for ectopic pregnancy as a result of IVF treatment were evaluated; the study included women who had an unruptured ectopic pregnancy after IVF treatment that was treated with either MTX or laparoscopic salpingectomy and underwent a subsequent IVF cycle. The main outcome measures were baseline serum FSH concentrations and ovarian response in the subsequent IVF cycle after treatment of ectopic pregnancy. Of a total of 58 patients, 36 were previously treated with MTX and 22 others by salpingectomy. No significant differences were observed between the MTX and the salpingectomy groups in the parameters of ovarian response in the subsequent IVF cycle.

The effect of bladder fullness on evaluation of pelvic organ prolapse.

OBJECTIVE: To investigate the effect of bladder fullness on pelvic organ prolapse (POP) staging via the Pelvic Organ Prolapse Quantification System (POP-Q). METHODS: Sixty women with advanced POP underwent pelvic examination with maximal Valsalva straining via POP-Q with an empty bladder and after transcatheter bladder filling to maximum cystometric capacity, with simultaneous intra-abdominal and intravesical pressure recordings. Main outcome measures included POP-Q values and staging with full versus empty bladder. RESULTS: An empty bladder was associated with a significantly higher POP-Q staging (median, 3 vs 2; P<0.0001); and a lower location of points Ba (4.51 vs 1.37; P<0.0001), Aa (2.58 vs 0.62; P<0.0001), Bp (-0.68 vs -1.10; P=0.01), Ap (0.83 vs -1.27; P=0.002), C (1.57 vs -1.07; P<0.0001), and D (0.14 vs -2.77; P<0.0001) compared with a full bladder. However, genital hiatus, perineal body, and total vaginal length values were not significantly affected by bladder fullness. No differences in intra-abdominal or detrusor pressures were noted between empty and full bladder states. CONCLUSION: POP-Q assessment with a full bladder is associated with underestimation of POP severity. Therefore, bladder emptying should be a standard requirement for POP-Q staging and reporting.

Normal fasting plasma glucose levels during pregnancy: a hospital-based study.

OBJECTIVE: Recently, the International Association of Diabetes and Pregnancy Study Groups have suggested new criteria for the diagnosis of gestational diabetes including a fasting glucose level of ≥92 mg/dL. We determined reference levels for normal fasting plasma glucose levels throughout pregnancy and evaluated the new normal cut-off for fasting glucose level. METHODS: Charts of patients who delivered in our hospital between June 2001 and June 2006 were reviewed. Women with pregestational diabetes, fasting glucose level >105 mg/dL or delivery at <24 weeks were excluded. Fasting glucose levels were assessed in 11 time categories between three months prior and four months postpartum in 7946 women. RESULTS: Compared to preconception levels, fasting glucose levels decreased by a median of 3 mg/dL in the first trimester (81-78 mg/dL). During the third trimester a slight further glucose reduction was observed (median 76 mg/dL). After delivery fasting glucose levels increased sharply (84 mg/dL in the puerperium and 81 mg/dL by three months postpartum). Throughout pregnancy 5.2-9.0% of pregnant women had a fasting glucose level of ≥92 mg/dL [compared to 8.2% in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study]. CONCLUSION: Fasting glucose levels decrease early in pregnancy with only slight further decrease later on. It seems that the same fasting glucose cut-off can be used throughout pregnancy for the diagnosis of gestational diabetes mellitus.

Pregestational body mass index, weight gain during pregnancy and maternal hyperglycemia.

OBJECTIVE: To evaluate the associations between pregestational BMI and weight gain during pregnancy and the risk for maternal hyperglycemia. METHODS: The charts of all patients who delivered at our hospital between June 2001 and June 2006 were reviewed. Maternal hyperglycemia categories were defined as GDM (by the Carpenter and Coustan criteria); Impaired glucose tolerance (IGT - only one abnormal value in the 100 g OGTT); Abnormal GCT (≥140 mg/dL) but no high values on the OGTT. Women with GCT < 140 were defined as normal glucose tolerance (NGT). RESULTS: Pregravid BMI and glucose tolerance data were available for 9269 women. We also had data on weight gain during pregnancy for 7766 of these women. There was strong graded association between increasing BMI category and all levels of maternal hyperglycemia. There was significant negative correlation between BMI and weight gain during pregnancy (R = -0.251, P value < 0.0001). However, in the multivariate logistic regression model, only pregestational BMI was significantly associated with maternal hyperglycemia, whereas weight gain during pregnancy was no longer significant. CONCLUSIONS: Obesity is a strong predictor for gestational maternal hyperglycemia. Weight gain during pregnancy has less effect. Every effort should be made for pregestational weight reduction in overweight women.

First trimester fasting hyperglycemia as a predictor for the development of gestational diabetes mellitus.

OBJECTIVE: Screening for gestational diabetes mellitus (GDM) is usually done at 24-28 weeks of gestation. Our goal was to study the association between first trimester fasting plasma glucose level and GDM risk and to evaluate its efficacy as a screening test for GDM in comparison to a traditional risk factor, pregestational body mass index (BMI). STUDY DESIGN: The charts of all patients who delivered in our hospital between June 2001 and June 2006 were reviewed. Only subjects with a singleton pregnancy and a recorded first trimester fasting glucose level and BMI were studied. Women with pregestational diabetes mellitus, fasting glucose level >105mg/dl or delivery at <24 weeks were excluded. Screening properties of both fasting glucose level and BMI were calculated and compared using receiver operator characteristic curves. RESULTS: GDM was diagnosed in 135 of the 4876 women included in this study. Fasting glucose cut-off levels of 80-85mg/dl yielded sensitivities of 75-55% and specificities of 52-75% for GDM prediction. BMI cut-off values of 25-28 had sensitivities of 60-40% and specificities of 72-86% for GDM prediction. Receiver operator curves for fasting glucose levels and BMI showed similar performance in predicting GDM (area under curve 0.72±0.023 vs. 0.74±0.021 (P=0.44)). There was approximately a 1.5-fold increase in the risk of developing GDM with each 5mg/dl increase in fasting glucose or 3.5kg/m² increase in BMI. CONCLUSION: Higher first trimester fasting glucose levels, within the normoglycemic range, constitute an independent risk factor for the development of GDM among young pregnant women.

First-trimester fasting hyperglycemia and adverse pregnancy outcomes.

OBJECTIVE: The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study found strong associations between higher levels of maternal glucose at 24-32 weeks, within what is currently considered normoglycemia and adverse pregnancy outcomes. Our aim was to evaluate the associations between first-trimester fasting plasma glucose level and adverse pregnancy outcomes. RESEARCH DESIGN AND METHODS: Charts of all patients who delivered at our hospital between June 2001 and June 2006 were reviewed. Only subjects with singleton pregnancy and a recorded first-trimester fasting glucose level were included. Women with pregestational diabetes, fasting glucose level >105 mg/dl, or delivery <24 weeks were excluded. Fasting glucose levels were analyzed in seven categories, similar to the HAPO study. The main outcomes were development of gestational diabetes mellitus (GDM), large-for-gestational-age (LGA) neonates and/or macrosomia, and primary cesarean section. Multivariate logistic regression analysis was used; significance was <0.05. RESULTS: A total of 6,129 women had a fasting glucose test at median of 9.5 weeks. There were strong, graded associations between fasting glucose level and primary outcomes. The frequency of GDM development increased from 1.0% in the lowest glucose category to 11.7% in the highest (adjusted odds ratio 11.92 [95% CI 5.39-26.37]). The frequency of LGA neonates and/or macrosomia increased from 7.9 to 19.4% (2.82 [1.67-4.76]). Primary cesarean section rate increased from 12.7 to 20.0% (1.94 [1.11-3.41]). CONCLUSIONS: Higher first-trimester fasting glucose levels, within what is currently considered a nondiabetic range, increase the risk of adverse pregnancy outcomes. Early detection and treatment of women at high risk for these complications might improve pregnancy outcome.