Does fresh single embryo transfer outcome predict the result of a subsequent vitrified-warmed blastocyst of the same cohort?

Reflecting the current trends, the utilization of frozen-thawed transfer cycles has been steadily increasing worldwide; outcome predictors of these cycles are therefore a major research goal. Our aim was to investigate whether the outcome of a fresh single blastocyst transfer (SBT) can serve as a prognostic factor for the subsequent vitrified-warmed SBT originating from the same cohort. A retrospective cohort study was performed at a single unit. Non-donor fresh cycles were analyzed as predictors of the following vitrified-warmed cycle. Only SBTs were included. Cycles designated to a freeze-all policy and cycles involving pre-implantation genetic analysis were excluded. A total of 1127 vitrified-warmed single blastocyst cycles were included. The indications for artificial reproductive technologies were comparable across the study groups. Vitrified-warmed cycles following a live birth outcome in the fresh cycle were more likely to result in a clinical pregnancy than those following a fresh cycle, which failed to reach a live birth. The same trend was observed for live birth rate following vitrified-warmed transfer in the fresh cycle. After correcting for possible confounders, age and embryo quality were significantly correlated with the chance for a live birth, but the previous fresh cycle did not affect the results. We therefore conclude that after adjustment for age, embryo quality and number of previous oocyte retrieval cycles, the fresh cycle outcome was not a significant influential factor for the following vitrified-warmed cycle.

A decision tree model for predicting live birth in FMR1 premutation carriers undergoing preimplantation genetic testing for monogenic/single gene defects.

RESEARCH QUESTION: Can patient selection for successful preimplantation genetic testing for women who are fragile X (FMR1) premutation carriers be optimized using a decision tree analysis? This decision support tool enables a comprehensive study of a set of clinical parameters and the expected outcomes. DESIGN: A retrospective case-control study analysing the results of 264 fresh and 21 frozen preimplantation genetic testing for monogenic disorders/single gene defects (PGT-M) cycles in 64 FMR1 premutation carriers. Primary outcome was live birth per cycle start. Live birth rate was calculated for the start of the ovarian stimulation cycle. Fresh and frozen embryo transfers from the same cycle were included. RESULTS: The decision tree model showed that the number of cytosine guanine (CGG) repeats was only a moderate predictor for live birth, whereas an age younger than 36 years was the best predictor for live birth, followed by a collection of 14 or more oocytes. These findings were supported by the results of the logistic regression, which found that only age and oocyte number were significantly associated with live birth (P = 0.005 and 0.017, respectively). CONCLUSIONS: The number of CGG repeats is a relatively poor predictor for live birth in PGT-M cycles. FMR1 premutation carriers are no different from non-carriers. Age is the best identifier of live birth, followed by the number of retrieved oocytes.

In-vitro maturation of oocytes recovered during cryopreservation of pre-pubertal girls undergoing fertility preservation.

RESEARCH QUESTION: In-vitro maturation (IVM) of oocytes recovered during ovarian tissue cryopreservation (OTC) is often practised, although it is still considered experimental. To date, only a few studies have examined the success of this maturation process in pre-menarche girls. The aim of this study was to examine the outcomes of IVM of oocytes recovered during OTC in pre-menarche patients scheduled for onco-therapy. DESIGN: A retrospective cohort study in a tertiary university-affiliated hospital. A total of 93 patients aged 0-25 years who underwent OTC as part of onco-fertility preservation between 2007 and 2019 were included in the study. Oocytes were recovered from the medium after OTC and matured over 48 h. Oocyte development and maturation rate were recorded and compared between different age groups. RESULTS: Patient's age was not correlated linearly with the total number of mature oocytes R = 0.2. The absolute maturation rate in post-menarche and pre-menarche patients differed significantly (38.0% versus 25.3%, respectively; P > 0.001), whereas the degeneration rate of the oocytes did not (39.8% versus 33.5%; P = 0.167). The pre-menarche group had significantly lower mean number of metaphase II oocytes compared with the post-menarche group (2.8 [±2.3] versus 5.6 [±4.6]; P = 0.01; 95% CI -4.62 to -0.46). Oocytes recovered from patients aged 1-5 years demonstrated low maturation rate. CONCLUSIONS: Oocytes recovered from pre-menarche girls, and especially those younger than the age of 5 years who undergo fertility preservation, have a lower chance of reaching maturity in IVM compared with older women. This may indicate a need for alternative methods for preserving fertility in these young patients.

Ovarian stimulation outcomes among transgender men compared with fertile cisgender women.

PURPOSE: To compare assisted reproductive technology (ART) outcomes among transgender men with those of fertile cisgender women. METHODS: This retrospective cohort study included 12 transgender men, six with no testosterone exposure and six after testosterone treatment, and 12 cisgender women (oocyte donors) who underwent ART in our institution between June 2017 and December 2019. Statistical analyses compared ART data and outcomes between three groups: cisgender women, transgender men without testosterone exposure, and transgender men after testosterone exposure. Comparisons were also made between transgender men with and without testosterone exposure. RESULTS: The transgender men with no testosterone exposure (23.3 ± 4 years) were significantly younger than the transgender men who had undergone testosterone treatment (30.3 ± 3.8 years; P = 0.012) and the cisgender women (29.1 ± 3.1 years; P = 0.004). The amount of FSH used for ovulation induction (1999 ± 683 mIU/mL) was significantly lower among transgender men without prior testosterone exposure compared with that among cisgender women (3150 ± 487 mIU/mL; P = 0.007). There were no differences in the peak estradiol levels, the number of oocytes retrieved, the number of MII oocytes, and the oocyte maturity rates between the three groups. Five out of six testosterone-treated transgender men underwent embryo cryopreservation, and they all achieved good-quality embryos. CONCLUSIONS: Transgender men have an excellent response to ovulation stimulation even after long-term exposure to testosterone. Oocyte/embryo cryopreservation is, therefore, a feasible and effective way for them to preserve their fertility for future biological parenting.

Oocyte Donation From Donor Older Than 35 Years. Is It Worth Trying?

INTRODUCTION: Due to several reasons, in some countries commercial oocyte donation is not possible. Accordingly, patients should find their own donors who may be over 35 years. The aim of this study was to compare the results of oocyte donation from donors <35 years (young donors) and donors ≥35 years old (older donors). MATERIAL AND METHODS: A retrospective cohort study was conducted at a single academic reproductive center. We compared the results of oocyte donation from donors <35 years (345 cycles) and from donor ≥35 years old (83 cycles). We also performed subgroup analysis for single embryo transfer (SET) and fresh and frozen embryo transfers. RESULTS: Recipient demographic characteristics of the 2 groups were comparable. The age of the donors was 29.8 ± 3.9 years in the young donor group and 37.6 ± 2.1 years in the older donor group ( P < .0001). Pregnancy and implantation rates in the recipients from young donor group were statistically significantly higher than those from the older donor group (50.7% and 40.9% vs 38.3% and 23%; P = .04, P < .001). Cumulative pregnancy and live birth rates were significantly higher in the young donor group compared to the older donor group (86.1% vs 57.4% P < .0001 and 52.2% vs 33.3%, P = .02, respectively). Subgroup analysis showed comparable pregnancy and live birth rates for SET cycles (45.5% vs 40.4% and 25.0% vs 21.2%, respectively) and fresh cycles (54.7% vs 42.6% and 35.8% vs 29.6%, respectively). CONCLUSION: In nonanonymous oocyte donation programs, donation from older donors with good ovarian reserve is an acceptable approach when young donor is not available.

Time-lapse imaging reveals delayed development of embryos carrying unbalanced chromosomal translocations.

PURPOSE: The purpose of the study was to compare the morphokinetic parameters of embryos carrying balanced chromosomal translocations with those carrying unbalanced chromosomal translocations using time-lapse microscopy. METHODS: The study group included 270 embryos that underwent biopsies on day 3 for preimplantation genetic diagnosis (PGD) for chromosomal translocations in our unit between 2013 and 2015. All embryos were incubated under time-lapse microscopy and evaluated for timing of developmental events up to day 5. The timing of these events was compared between balanced and unbalanced embryos, potentially viable and nonviable variants, and maternal versus paternal inheritance of the translocation. RESULTS: The PGD analysis found that 209 (77%) of the 270 biopsied embryos carried an unbalanced translocation. Embryos carrying unbalanced translocations, which are expected to lead to implantation failure or miscarriage, cleaved less synchronously and were delayed in time of cleavage to the 4-cell stage (t4) and in time of start of blastulation (tSB) compared with balanced embryos (P < 0.05). Furthermore, embryos carrying nonviable translocations demonstrated a significant delay at the time of pronuclei fading (tPNf) compared with those carrying potentially viable translocations (P < 0.05). Embryos whose unbalanced translocations were of maternal origin were significantly delayed in most of the morphokinetic parameters (including tPNf, t2, t3, t4, t6, t7, t8, cc2, s2, and tSB) compared with embryos carrying balanced translocations (P < 0.05). CONCLUSIONS: Embryos carrying unbalanced chromosomal translocations mainly of maternal origin undergo delayed development and asynchronous cleavage that may lead to implantation failure or miscarriage.

The Effect of Intramural Myomas Without an Intracavity Component on In Vitro Fertilization Outcomes in Single Fresh Blastocyst Transfer Cycles.

STUDY OBJECTIVE: To assess clinical pregnancy rate (CPR) and live birth rate (LBR) in the presence of non-cavity-deforming intramural myomas in single fresh blastocyst transfer cycles. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Academic fertility center. PATIENTS: A total of 929 fresh single blastocyst transfer cycles were included, 94 with only non-cavity-distorting intramural myomas and 764 without myomas. Cleavage embryo transfers were excluded to reduce bias based on embryo quality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CPR and LBR were assessed. There were no differences noted in gravidity, parity, or body mass index between patients with myomas and those without myomas. Women with myomas required higher doses of gonadotropins (mean, 2653 ± 404 IU vs 2350 ± 1368 IU; p = .04) than women without myomas. However, the total number of mature oocytes collected and the total number of blastocysts created were similar. CPR (47% vs 32%; p = .005) and LBR (37.8% vs 25.5%; p = .02) were lower in patients who had intramural myomas compared with those without myomas. CPR and LBR were significantly reduced in the presence of even 1 myoma (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33-0.83 and OR, 0.56; 95% CI, 0.35-0.92, respectively). In patients with myomas >1.5 cm, LBR was also significantly reduced, even after adjusting for age, smoking, quality of embryo transferred, antral follicle count, and dose of gonadotropins (OR, 0.53; 95% CI, 0.29-0.97). This LBR finding was not significant if all myomas were included (including those <1.5 cm in diameter), but CPR was still significantly reduced. CONCLUSION: Relatively small (>1.5 cm) non-cavity-distorting intramural myomas negatively affect CPR and LBR in in vitro fertilization cycles, even in the presence of only 1 myoma.

Do trained reproductive endocrinologists perform better than their trainees? Comparing clinical pregnancy rates and live birth rates after transfer of single fresh blastocysts.

PURPOSE: To compare clinical pregnancy rates and live birth rates of single blastocyst transfers performed by attending physicians or fellows in reproductive endocrinology and infertility program. METHODS: Retrospective study in an academic reproductive center. We evaluated 932 fresh single blastocyst transfer cycles performed by fellows in training (389 embryo transfers) and by attending physicians (543 embryo transfers). RESULTS: There were no differences in the baseline characteristics and IVF cycle parameters between patients who had transfers performed by fellows or attending physicians. Transfers performed by attending physicians or fellows resulted in similar CPR (46.5 vs. 42.9%, p = 0.28) and LBR (38.3 vs. 34.2%, p = 0.11). Multivariate logistic regression analysis showed that even after adjusting for possible confounders (age, gravity, parity, baseline FSH, antral follicle count, dose of gonadotropins, stimulation protocol, and quality of embryo transferred), CPR (OR 0.81, CI 0.62-1.07) and LBR (OR 0.79, CI 0.6-1.05) in the two groups were comparable. CONCLUSION: Clinical pregnancy rate and live birth rate after embryo transfer performed by attending staffs or fellows are comparable. This finding reassures fellowship programs that allowing fellows to perform embryo transfers does not compromise the outcome.

Obstetric and neonatal outcomes of pregnancies conceived after preimplantation genetic diagnosis: cohort study and meta-analysis.

Preimplantation genetic diagnosis (PGD) may pose risks to pregnancy outcome owing to the invasiveness of the biopsy procedure. This study compares outcome of singleton and twin clinical pregnancies conceived after fresh embryo transfers of PGD (n = 89) and matched intracytoplasmic sperm injection (ICSI) pregnancies (n = 166). The study was carried out in a single university affiliated centre. Because of the paucity of available data, a literature-based meta-analysis of studies comparing neonatal outcome of PGD and ICSI pregnancies was also conducted. In the retrospective cohort study, obstetric and neonatal outcome were available in 67 PGD and 118 ICSI pregnancies. Perinatal outcomes were comparable between PGD and ICSI pregnancies. Meta-analysis revealed similar outcomes, except for higher rate of low birth weight (<2500 g) neonates in ICSI twin pregnancies (RR 0.86, 95% CI 0.74 to 1.0). Mean birth weight, gestational age at birth, pre-term deliveries (<37 weeks) and malformations were all comparable. In this cohort study and subsequent meta-analysis, no association was found between PGD conceived pregnancies and risks of adverse neonatal or obstetrical outcomes compared with ICSI pregnancies. Hence, blastomere biopsy for PGD does not seem to increase the risk for adverse perinatal outcome compared with ICSI pregnancies.

The effect of endometrial injury on implantation and clinical pregnancy rates.

AIM: To assess the effect of endometrial scratching (ES) on in vitro fertilization-embryo transfer outcome (IVF-ET) Materials and methods: Retrospective matched case control study including all fresh IVF cycles performed between January 2006 and December 2012 at an academic IVF center. ES with an endometrial biopsy catheter was performed in the cycle preceding the index IVF cycle. Patients (n = 238) were pair matched with controls according to age, number of previous failed IVF cycles and number of embryos transferred. RESULTS: Demographic and cycle characteristics were comparable in all of the following: age, number of previous cycles, number of collected oocyte, number of embryos transferred and quality of transferred embryos. Implantation, clinical and ongoing pregnancy rates were comparable in both groups (28%, 34% and 18.4% vs 30%, 40.3% and 29%, in ES group and controls, respectively). Logistic regression analysis found no significant association between ES and pregnancy rate. CONCLUSIONS: Mechanical endometrial stimulation did not improve implantation and pregnancy rates. Furthermore, no factors that may predict which patients could benefit from ES were identified. Further prospective studies are warranted to evaluate possible benefits in different subsets of patients such as patients with recurrent implantation failures.

Reproductive outcomes of familial oocyte donation.

OBJECTIVE: Oocyte donation (OD) from a family member may be more available to patients. Our objective was to compare reproductive outcomes of familial OD with those of unrelated OD. DESIGN: Retrospective cohort study in a single university-affiliated center. SETTING: Not applicable. PATIENT(S): Four hundred thirty OD cycles performed from 2010 to 2014: 124 from family members and 306 from unrelated donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ovarian stimulation parameters and cycle outcomes (total gonadotropin dose, number of retrieved oocytes, number of embryos, number of vitrified embryos, blastocyst transfer rate, rate of fresh transfers); endometrial preparation parameters; implantation, clinical pregnancy, miscarriage, and live birth rates; perinatal outcomes (gestational age at birth, birth weight, delivery mode, cesarean delivery rates). RESULT(S): Implantation, clinical pregnancy, miscarriage, and live birth rates were similar between familial OD cycles and unrelated OD cycles (32.9% vs. 39.7%, 41.9% vs. 44.4%, 30.7% vs. 30.9%, and 29% vs. 28.7%, respectively). Gestational age at birth and birth weight were similar (37.8 wk ± 2.2 d vs. 37.1 wk ± 3 d and 3,043 ± 722 g vs. 2,906 ± 788 g, respectively). Similar outcomes were also found in single-embryo transfer OD cycles (live birth rate 26.7% vs. 24.2%). Sister-to-sister OD cycles outcomes were similar to those of unrelated donors. CONCLUSION(S): The reproductive outcomes of familial OD are similar to those of unrelated OD. These findings are in contrast to previous presumptions regarding the efficiency of familial OD and may help in the counseling of women who need OD.

Cabergoline for reducing ovarian hyperstimulation syndrome in assisted reproductive technology treatment cycles. A prospective randomized controlled trial.

OBJECTIVE: To investigate whether cabergoline (Cb2), a dopamine agonist, reduces ovarian hyperstimulation syndrome (OHSS) in high-risk women undergoing assisted reproductive technology (ART), and to analyze whether cabergoline affects the outcome of ART. STUDY DESIGN: Forty infertile women at risk of developing OHSS were enrolled in the trial. The inclusion criteria were as follows: infertile women undergoing IVF with serum estradiol concentration > 4,000 pg/mL or with > 20 follicles > 12 mm on the day of human chorionic gonadotropin (hCG) administration, and 18-40 years of age. They were randomized into 2 groups: the Cb2 group (n = 20) received 0.5 mg oral Cb2 per day for 8 consecutive days beginning on the day of hCG, and the control group (n = 20) received no medication. RESULTS: Ascites was significantly lower (p = 0.008) in the Cb2 group as compared with the control group. The incidence of moderate OHSS was also significantly lower (p = 0.04) in the Cb2 as compared to the control group. There was no evidence of statistically significant differences regarding the parameters of ART outcome. CONCLUSION: Our data supports the use of Cb2 in the management of high-risk women undergoing ART and, consequently, achieving lowered risk of OHSS, with no deleterious impact on ART outcomes.

Obstetricians and gynecologists: which characteristics do Israeli lesbians prefer?

AIM: The aim of this study was to explore lesbians' preferences when choosing obstetricians/gynecologists. MATERIAL AND METHODS: This cross-sectional study included 100 lesbian and 100 heterosexual women. A 40-item questionnaire assessed the correlation between a patient's sexual identity and her specific preferences for obstetricians/gynecologists. RESULTS: The top five most important parameters for both groups in choosing obstetricians/gynecologists overlapped greatly. Four of those were experience, ability, knowledge and personality. Only one parameter differed: lesbians ranked 'sexually tolerant' as the third most important characteristic while heterosexuals ranked 'availability' as the fifth most important characteristic. Lesbians rated 'sexual tolerance' significantly higher than heterosexuals (P < 0.001). More lesbians (56%) preferred female obstetricians/gynecologists compared to heterosexuals (21%) (P < 0.001). When compared to heterosexuals, more lesbians preferred female obstetricians/gynecologists for intimate and non-intimate procedures (P < 0.001). But within the lesbian population, a higher percentage of subjects showed a preference for female obstetricians/gynecologists only for intimate procedures. Lesbians used the following to describe their preference for female obstetricians/gynecologists: feeling more comfortable; gentle; sympathetic; patient; more understanding of women's health; better physicians in general; and more sexually tolerant (P < 0.001 vs heterosexual). However, when we looked only at the lesbian population, the majority did not exhibit a preference for a female obstetrician/gynecologist for any of these reasons. The main reason given by the 56% of the lesbians who said they prefer female obstetricians/gynecologists was feeling more comfortable. CONCLUSION: Overwhelmingly lesbians prefer sexually tolerant obstetricians/gynecologists regardless of their gender; however, only a small number of lesbian subjects in this study considered their obstetricians/gynecologists as displaying this characteristic.

Total fertilization failure in intra-cytoplasmic sperm injection cycles--classification and management.

In this retrospective cohort study we intended to propose a classification and preliminary management strategy for couples exhibiting total fertilization failure (TFF) in intra-cytoplasmic sperm injection (ICSI) cycles. Sixteen couples with a total of 27 cycles exhibiting TFF, age <40 and/or more than four M2 oocytes aspirated were enrolled. While TFF occurred in 4.3% of all 3723 ICSI cycles, in women younger than 40 with at least 5 M2 oocytes the TFF rate was 0.7%. Indications for ICSI were severe male factor and unexplained infertility. Of the 16 couples with TFF, 4 demonstrated a single episode of TFF, with either subsequent or former normal fertilizations, thus implying possible sporadic faulty laboratory conditions. Ten couples demonstrated repeated total or very low fertilization rates, hinting at a gamete defect not overcome by ICSI. Two couples experienced TFF in the first and only cycle performed at our unit. We conclude that initial and repeated TFF hints at severe gamete defects for which only donor gametes may prove successful while sporadic TFF events could simply imply a technical modifiable condition.

Adnexal torsion: cystectomy and ovarian fixation are equally important in preventing recurrence.

OBJECTIVE: To report our clinical experience in adnexal torsion. STUDY DESIGN: A retrospective case review of surgically proven adnexal torsion. RESULTS: 216 cases were identified. Mean age was 29±12. Twenty-two were premenarchal, 59 had ovarian stimulation, 48 were pregnant (with a median gestational age of 7 weeks) and 14 were post-menopausal. The most common risk factor was a previous history of adnexal torsion. The main clinical features were sudden, intermittent pain. Forty-five percent of Doppler examinations demonstrated normal flow: premenarchal and postmenopausal patients had higher rates of abnormal flow, compared to pregnant patients or after ovarian stimulation. Median time from admission to diagnosis was 6 h. Laparoscopy was conducted in 81.0% of the cases, and laparotomy in the rest. Twenty-three cases of recurrent torsion were documented. The majority of these events occurred following detorsion only. An enlarged ovary was found in 77 cases, dermoid cyst in 8 cases, and one case was malignant. Sixty eight-cases underwent detorsion, in 82 cases a combined detorsion and cystectomy or fenestration were performed and 43 patients underwent partial or total adnexectomy. Adnexal fixation was conducted in 21 cases. Cyst drainage or cystectomy significantly reduced the chance of retorsion by 50% and 75%, respectively, compared to detorsion only. CONCLUSION: Ovarian stimulation and early pregnancy are predisposing factors for ovarian torsion. Doppler flow studies may be a helpful diagnostic tool among premenarchal and post-menopausal women. Cystectomy should be considered in order to reduce the risk of retorsion.

Risk factors, symptoms, and treatment of ovarian torsion in children: the twelve-year experience of one center.

OBJECTIVE: To assess risk factors, clinical findings and mode of diagnosis and treatment in premenarchal children with surgically verified ovarian torsion (OT). STUDY DESIGN: A retrospective case review (Canadian Task Force Classification II-2). SETTING: Teaching and research hospital, a tertiary center. PATIENTS: Premenarchal children with surgically verified OT. INTERVENTIONS: Patients underwent either laparoscopy or laparotomy. RESULTS: Twenty-two cases of OT in 20 premenarchal girls (median age 12 years) were identified. Three cases involved recurrent torsion after detorsion without cystectomy. The main presenting symptoms were sudden pain and vomiting. Six patients underwent Doppler examinations, and all demonstrated an abnormal flow. Seventeen interventions were by laparoscopy. Conservative management, mainly detorsion with additional cyst drainage or cystectomy, was performed in 19 cases (86.4%). Oophoropexy was performed in 3 cases (13.6%). Pathologic examination demonstrated 5 simple cysts and 1 dermoid cyst. CONCLUSIONS: Ovarian torsion in premenarchal girls usually presents with intermittent abdominal pain and abdominal tenderness. Other signs and symptoms are nonspecific. When performed, Doppler imaging may assist in diagnosing ovarian torsion in children. Detorsion followed by cystectomy may prevent recurrence.

Reduction of twin pregnancy to singleton: does it improve pregnancy outcome?

OBJECTIVE: To compare pregnancy complications, obstetrical and neonatal outcome of twin pregnancies reduced to singleton, with both non-reduced twin pregnancies and singleton pregnancies. METHODS: A retrospective case-control study was performed at the Obstetrics and Gynecology Ultrasound unit of a tertiary referral medical center. Patient's population included 32 bi-chorionic bi-amniotic twin pregnancies reduced to singleton and 35 non-reduced twin pregnancies. Thirty-six patients with singleton pregnancies comprised the second control group. Main outcome measures were rates of pregnancy complications, preterm delivery (both before 37 weeks of gestation and before 34 weeks of gestation), late abortions, intra-uterine growth retardation, cesarean section, mean birth weights, and mean gestational age at delivery. RESULTS: The reduced twin pregnancies group had similar rates of total pregnancy complications, preterm deliveries, and cesarean section as non-reduced twins. Gestational age at delivery and mean birth weight were also similar to non-reduced twins and significantly different compared with singletons. Preterm delivery and late abortion incidences were significantly higher when reduction was beyond 15 weeks gestation. CONCLUSIONS: Reduction of twin pregnancy to singleton does not change significantly pregnancy course and outcome. Favorable obstetrical and neonatal outcomes could be achieved by performing early, first trimester reductions.

Third- and fourth-degree perineal tears: prevalence and risk factors in the third millennium.

OBJECTIVE: We sought to assess the modern prevalence and risk factors for third- and fourth-degree perineal tears. STUDY DESIGN: The study population comprised 38,252 women who delivered in one medical center, from January 2005 through December 2009, and met the following inclusion criteria: singleton pregnancy, vertex presentation, and vaginal delivery. Of these, 96 women (0.25%) sustained third- or fourth-degree perineal tears. Maternal and obstetric variables were compared between women with vs without severe perineal tears. RESULTS: Five variables were found to be statistically significant independent risk factors: Asian ethnicity (odds ratio [OR], 8.9; 95% confidence interval [CI], 4.2-18.9), primiparity (OR, 2.4; 95% CI, 1.5-3.7), persistent occipito posterior (OR, 2.1; 95% CI, 1-4.5), vacuum delivery (OR, 2.7; 95% CI, 1.6-4.6), and heavier birthweight (OR, 1.001; 95% CI, 1-1.001). CONCLUSION: Severe perineal tears are uncommon in modern obstetric practice. Significant risk factors are Asian ethnicity, primiparity, persistent occipito posterior, vacuum delivery, and heavier birthweight.

The effect of herpes simplex virus-1 on nitric oxide synthase in the rat brain: the role of glucocorticoids.

OBJECTIVE: Herpes simplex virus-1 (HSV-1) is a common cause of viral encephalitis manifested by activation of the adrenocortical axis, fever and behavioral changes. We investigated the early effects of HSV-1 on constitutive (c) and inducible (i) nitric oxide synthase (NOS) activity in rat brain and in mixed glial cell culture. The effect of glucocorticoids (GCs) on NOS responses to HSV-1 was also determined. METHODS: NOS activity was evaluated by the conversion of ³H-arginine to ³H-citrulline. Nitrites were measured in supernatants of activated glial cells. RESULTS: Under basal conditions, the highest cNOS activity was found in the cerebellum, while activity was much lower in the pons and negligible in the hypothalamus and hippocampus. Forty-eight hours after intracerebral injection of HSV-1, serum corticosterone was increased and NOS activity in the cerebellum and pons was inhibited. Adrenalectomy had no effect on the basal NOS activity but completely abrogated the inhibitory effect of HSV-1. Administration of the iNOS inhibitor aminoguanidine did not significantly change NOS activity, suggesting that the activity found in the cerebellum and pons can be attributed to the cNOS isoform. In mixed glial cell culture infected with HSV-1 and then activated with lipopolysaccharide, NOS activity and nitrite production were inhibited by 77 and 53%, respectively. CONCLUSIONS: These results suggest that brain NOS activity is inhibited in the early stages of HSV-1 infection and requires the presence of circulating GCs. HSV-1-induced brain NOS inhibition may play a role in neuronal viral invasion and in the activation of the adrenocortical axis.

Invasive pediatric Kingella kingae Infections: a nationwide collaborative study.

BACKGROUND: Kingella kingae is a gram-negative coccobacillus, increasingly recognized as an invasive pediatric pathogen. To date, only few small series of invasive K. kingae infections have been published, mostly from single medical centers. A nationwide multicenter study was performed to investigate the epidemiologic, clinical, and laboratory features of children with culture-proven K. kingae infections. METHODS: Clinical microbiology laboratories serving all 22 medical centers in Israel were contacted in a search for children aged 0 to 18 years from whom K. kingae was isolated from a normally sterile site, dating from as far back as possible until December 31, 2007. Medical records of identified patients were reviewed using uniform case definitions. RESULTS: A total of 322 episodes of infection were identified in 321 children, of which 96% occurred before the age of 36 months. The annual incidence in children aged <4 years was 9.4 per 100,000. Infections showed a seasonal nadir between February and April. Skeletal system infections occurred in 169 (52.6%) children and included septic arthritis, osteomyelitis, and tenosynovitis. Occult bacteremia occurred in 140 children (43.6%), endocarditis in 8 (2.5%), and pneumonia in 4 (1.2%). With the exception of endocarditis cases, patients usually appeared only mildly ill. About one-quarter of children had a body temperature <38 degrees C, 57.1% had a blood white blood cell count <15,000/mm, 22.0% had normal C-reactive protein values, and 31.8% had nonelevated erythrocyte sedimentation rate. CONCLUSIONS: K. kingae infections usually occur in otherwise healthy children aged 6 to 36 months, mainly causing skeletal system infections and bacteremia, and occasionally endocarditis and pneumonia. Clinical presentation is usually mild, except for endocarditis, necessitating a high index of suspicion.