Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging.

Female reproductive capacity declines dramatically in the fourth decade of life as a result of an age-related decrease in oocyte quality and quantity. The primary causes of reproductive aging and the molecular factors responsible for decreased oocyte quality remain elusive. Here, we show that aging of the female germ line is accompanied by mitochondrial dysfunction associated with decreased oxidative phosphorylation and reduced Adenosine tri-phosphate (ATP) level. Diminished expression of the enzymes responsible for CoQ production, Pdss2 and Coq6, was observed in oocytes of older females in both mouse and human. The age-related decline in oocyte quality and quantity could be reversed by the administration of CoQ10. Oocyte-specific disruption of Pdss2 recapitulated many of the mitochondrial and reproductive phenotypes observed in the old females including reduced ATP production and increased meiotic spindle abnormalities, resulting in infertility. Ovarian reserve in the oocyte-specific Pdss2-deficient animals was diminished, leading to premature ovarian failure which could be prevented by maternal dietary administration of CoQ10. We conclude that impaired mitochondrial performance created by suboptimal CoQ10 availability can drive age-associated oocyte deficits causing infertility.

Can cycle day 7 FSH concentration during controlled ovarian stimulation be used to guide FSH dosing for in vitro fertilization?

BACKGROUND: When stimulating a patient with poor ovarian response for IVF, the maximal dose of gonadotropins injected is often determined by arbitrary standards rather than a measured response. The purpose of this study was to determine if serum FSH concentration during an IVF stimulation cycle reflects follicular utilization of FSH and whether serum FSH values may inform dose adjustments of exogenous FSH. METHODS: In this retrospective cross sectional study we studied 155 consecutive IVF cycles stimulated only with recombinant human FSH. We only included long GnRH agonist protocols in which endogenous FSH levels were suppressed. We correlated the serum concentration of cycle day (CD) 7 FSH with the number of oocytes retrieved, cleaving embryos and pregnancy rate. RESULTS: We found that a CD7 FSH concentration above 22 IU/L was associated with poor response regardless of the daily dose of FSH injected and a lower pregnancy rate. CONCLUSIONS: We concluded that CD7 FSH concentration during stimulation could be used to guide FSH dosing in poor responders. If the CD7 FSH concentration is above 22 IU/L increasing the dose of FSH in an attempt to recruit more growing follicles is unlikely to be successful.

The effects of low-level laser light exposure on sperm motion characteristics and DNA damage.

The objective of this study was to determine the effects of low-level laser light exposure on the motility of spermatozoa and on DNA damage. Thirty-three semen samples were collected for routine analysis and were classified as normospermic, oligospermic, or asthenospermic. After routine semen analysis was performed, residual semen was divided into treated and control aliquots. Treated samples were exposed to a 30-second infrared laser pulse of 50 mW/cm(2) at 905 nm, a wavelength thought to increase light-sensitive cytochrome c oxidase in the mitochondrial electron transport chain. Samples were then incubated at 37°C, and aliquots were analyzed at 30 minutes and 2 hours using computerassisted semen analysis. After incubation, 250 µL of each sample was frozen at 280°C until DNA fragmentation analysis by flow cytometry. A significant increase in motility, most prominent in oligospermic and asthenospermic samples (85% increase), was observed 30 minutes after the treatment (P < .0001). No significant increase in DNA damage compared with control samples was observed. Significant changes in sperm motion kinetics were observed. Low-level laser light exposure appears to have a positive short-term effect on the motility of treated spermatozoa and did not cause any increase in DNA damage measured at 2 hours. We conclude that some cases of asthenospermia may be related to mitochondrial dysfunction. The implications of this study in terms of future clinical applications needs further investigation.

Use of letrozole challenge test to adjust gonadotropin dose in non-down-regulated cycles.

The use of a letrozole challenge test to predict ovarian response is described. The authors show that a ratio of cycle day 7 to cycle day 3 post-letrozole FSH level >1.5 is associated with poor ovarian response.

An ongoing pregnancy from two waves of follicles developing during a long follicular phase of the same cycle.

OBJECTIVE: To report an ongoing pregnancy after in vitro fertilization (IVF) with ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist that resulted in two waves of follicular growth. DESIGN: Case report. SETTING: University of Toronto affiliated infertility clinic. PATIENT(S): A 33-year-old woman with a 3-year history of secondary infertility. INTERVENTION(S): In vitro fertilization and embryo transfer. MAIN OUTCOME MEASURE(S): Ongoing pregnancy. RESULT(S): This patient successfully conceived after the GnRH antagonist-induced demise of the first cohort of follicles and the emergence of a second wave of follicles followed by oocyte retrieval on cycle day 30 and fresh embryo transfer. CONCLUSION(S): This case report is consistent with previous observations of multiple waves of follicle recruitment and growth per cycle. The window of implantation may not be adversely affected by prolonged or even variable estrogen exposure in the follicular phase of the cycle.

The use of mitochondrial nutrients to improve the outcome of infertility treatment in older patients.

We present a hypothesis emphasizing the role of mitochondrial dysfunction in reproductive senescence and suggesting the use of mitochondrial nutrients as an adjuvant treatment in older patients with infertility.

Three dimensional ultrasound diagnosis of caudal regression syndrome at 14 gestational weeks.

Caudal regression syndrome (CRS) is a rare complex abnormality, characterized by agenesis of the sacrum and lumbar spine, with lower limb neurological deficit and accompanying deformities of the pelvis, lower extremities, genitourinary, gastrointestinal and cardiac systems. Pregnancies complicated by insulin treated diabetes carry higher risk of fetal CRS than non-diabetic pregnancies. Three dimensional (3D) and four dimensional (4D) ultrasound may assist in early detection of CRS. We report a case of CRS diagnosed by 3D and 4D ultrasound examination at 14 weeks of gestation in a diabetic patient.

Three-dimensional placental volume measurements between 11 and 13 weeks' gestation.

We sought to determine whether three-dimensional (3D) placental volume measurements can be assessed in normal pregnancies between 11 and 13 weeks' gestation with good intraobserver accuracy. Twenty normal pregnancies were included. Placental volume was determined twice, using the virtual organ computer-aided analysis method. Three-dimensional placental volume measurements were performed by a single physician. Patients with multiple pregnancies, first-trimester bleeding, and abnormal placental appearance were excluded. Intraobserver reliability was evaluated by kappa analysis, and Student T test was performed for continuous variables. Mean placental volume (MPV) was 67.5 +/- 26.7 mL (3) between 11 and 13 weeks' gestation. No significant differences were noted between the two examinations performed (MPV of 67.5 +/- 26.7 mL (3) during the first versus 65.6 +/- 29.1 mL (3) during the second examination; p = 0.826). Moreover, the intraobserver agreement was excellent as indicated by kappa of 0.8. Placental volume can be assessed by 3D sonography between 11 and 13 weeks' gestation with minimal deviations. Nevertheless, the broad variability in placental volume with a wide standard deviation makes its clinical significance questionable.

Identifying risk factors for premature rupture of membranes in small for gestational age neonates: a population-based study.

OBJECTIVE: To determine the prevalence and risk factors for premature rupture of membranes (PROM) among pregnancies complicated with small for gestational age (SGA) neonates. METHODS: A computerised database was used to identify deliveries of SGA neonates in pregnancies complicated with PROM between the years 1988 and 2002. Pregnancies with PROM and SGA neonates were compared to those with SGA and without PROM. Demographic, obstetric, clinical and labour characteristics were evaluated. Multiple logistic regression analysis was used to determine independent risk factors for PROM in pregnancies complicated by SGA. Statistical analysis was performed with SPSS package. RESULTS: There were 120 982 deliveries included out of which 6074 (5.99%) presented with appropriate for gestational age (AGA) neonates and PROM. A total of 1077 delivered SGA infants complicated with PROM (5.5%). After adjustment for confounding variables, the following characteristics were significantly associated with PROM and SGA: Jewish ethnicity, parity and cervical incompetence. The following complications were associated with PROM and SGA: arrest of labour, fetal distress, failed induction, cesarean delivery, clinical chorioamnionitis and placenta accreta. No significant differences regarding low Apgar scores and perinatal mortality rates were noted. CONCLUSIONS: The risk of PROM among patients with SGA is lower than in AGA infants. Parity and cervical incompetence are risk factors for PROM among women who delivered SGA neonates. In this population there is a higher rate of arrest of labour, chorioamnionitis, fetal distress and cesarean delivery. Neonatal outcome and perinatal mortality are similar in both groups.

Pregnancy outcome among obese women: a prospective study.

We investigated pregnancy outcome among obese women using a prospective cohort study comparing consecutive deliveries of obese and nonobese patients. Stratified analysis, using the Mantel-Haenszel technique, was done to assess the association between obesity and the risk for cesarean delivery (CD) while controlling for confounding variables. Complete data were abstracted for 376 women, of whom 21% ( N = 79) were obese. CD rate was significantly higher among obese women (32.9% versus 18.9%; P = 0.006). Maternal obesity was associated with multiparity (odds ratio [OR] 2.97, 95% confidence interval [CI] 1.27 to 6.97; P = 0.012), fertility treatments (OR 11.3, 95% CI 2.84 to 44.89; P = 0.001), insulin-treated gestational diabetes (OR 24.55, 95% CI 2.28 to 264.08; P = 0.008), and hydramnios (OR 20.46, 95% CI 2.17 to 192.89; P = 0.008). When controlling for possible confounders, the association between maternal obesity and CD remained significant (weighted OR 2.2, 95% CI 1.2 to 4.1; P = 0.018). No significant differences were noted between the groups regarding neonatal complications. Both first and second stages of labor were longer in obese women. Obesity is a risk factor for developing gestational hypertension, insulin-treated gestational diabetes, and hydramnios. Moreover, maternal obesity is an independent risk factor for CD. Additional independent risk factors for CD were fertility treatments, insulin-treated gestational diabetes, and hydramnios. However, neonatal outcome of obese women is comparable to women with normal prepregnancy body mass index.

Face and brow presentation: independent risk factors.

OBJECTIVES: The objectives of this study were to determine clinical characteristics including pregnancy and delivery outcome, among patients with face/brow presentation, and to investigate independent risk factors for these malpresentations. METHODS: This was a retrospective cohort study comparing all singleton pregnancies of patients with and without face/brow presentation. Deliveries occurred during the years 1988-2002 at the Soroka University Medical Center. Stratified analyses using a multiple logistic regression model were performed to control for confounders. RESULTS: Two hundred and nineteen cases were included in the study out of 130,247 deliveries with vertex presentation, giving a prevalence for face/brow presentation of 0.17%. No significant difference was found with regard to maternal age and gravidity between the control and study groups, but the primiparity rate was lower in the study group (20.4% vs.14.6%, p = 0.034). There was a significantly higher rate of previous history of cesarean delivery (CD), polyhydramnios, non-progressive labor, and non-reassuring fetal heart rate in the study group, but the rate of hypertensive disorders was lower. The prevalence of congenital anomalies was higher in the study group than in the control group, 7.3% vs. 3.6%, respectively. Also the CD rate in the study group was 67.1% as compared to 8.6% in the control group (p < 0.001). In contrast, neonatal outcome was not different between groups, including Apgar scores and perinatal mortality (0.5% vs. 1.2%, p = NS). In a logistic regression analysis model for face/brow presentation, the independent risk factors were fetal malformations (OR = 2.0), polyhydramnios (OR = 2.77) and primiparity (OR = 0.65). CONCLUSION: Face/brow presentation was associated with several adverse pregnancy outcomes, although there was a favorable neonatal outcome. Independent risk factors for face/brow presentation were fetal malformations and polyhydramnios, but primiparity had a protective effect.

Clinical significance of uterine scar dehiscence in women with previous cesarean delivery: prevalence and independent risk factors.

OBJECTIVE: To determine the prevalence and risk factors for uterine scar dehiscence in women following cesarean delivery (CD). STUDY DESIGN: Our computerized database was used to identify patients with recurrent CDs in the index pregnancy (1988-2002). Women with uterine dehiscence were compared to those without dehiscence. Multiple logistic regression analysis was used to determine independent risk factors for dehiscence. RESULTS: Of 7,833 women with at least 1 previous CD and a CD in the index pregnancy, 81 (1.03%) had uterine scar dehiscence. This finding was associated with nonprogress of labor during the first stage, number of previous CDs, parity, preterm delivery and low Apgar scores at 5 minutes. For patients with only 1 previous CD, failure to progress during the first stage of labor and lower parity were associated with uterine scar dehiscence. The numbers of previous CDs, gravidity and placenta previa rate were significantly higher in the group with dehiscence who delivered preterm. CONCLUSION: Preterm delivery, nonprogress of labor during the first stage and number of previous CDs were found to be independent risk factors for uterine scar dehiscence. In contrast, parity had a protective effect against dehiscence.

Maternal and neonatal outcome following cerebrovascular accidents during pregnancy.

OBJECTIVE: To assess the clinical characteristics of maternal and neonatal outcome among women with cerebrovascular accidents (CVA) during pregnancy. METHODS: Our computerized database was used to identify patients with CVA during pregnancy and puerperium from January 1988 to March 2004. Their medical records were identified and reviewed. RESULTS: There were 16 cases of CVA among 173,803 deliveries, giving a risk of almost one case per 10,000 pregnant women. Out of 16 patients, 14 (88%) had a stroke and the remaining two cases were diagnosed with venous thrombosis. Of those 14 cases, nine (64%) had ischemic strokes and five (36%) had hemorrhagic strokes. Ten of the CVAs occurred antepartum, two intrapartum and four postpartum. Hypertensive disorders were diagnosed in 75% (12/16) of the patients. Out of these 12 patients with hypertension, 9 (75%) suffered from preeclampsia. One woman had a history of chronic hypertension. Smoking was associated with 63% (10/16) of the cases. There were two maternal deaths, both in women who had hemorrhagic strokes, and both in the first half of the study (1994 and 1996). Nine out of 16 women (56%), were delivered within 48 hours of the CVA including 7 (78%) antepartum, and two (22%) intrapartum. Cesarean deliveries were performed in 11/16 women (69%) including 8/10 with CVAs occurring antepartum, 1/2 intrapartum and 2/4 postpartum. One case of neonatal mortality was identified in a patient who was delivered at 24 gestational weeks. CONCLUSIONS: (1) Hypertensive disorders and smoking were the most important factors associated with CVA during pregnancy. (2) Maternal mortality was high among patients with CVA during pregnancy. (3) Neonatal outcome was considered generally good in cases of CVA.

[Fetal echogenic bowel by ultrasound: what is the clinical significance?].

Echogenic bowel is diagnosed in 0.2% to 1.4% of second trimester ultrasonographic examinations. This finding occurs as a normal variant in the second trimester but also has been associated with several pathologic conditions that include cystic fibrosis, chromosomal abnormalities and in utero infection with cytomegalovirus and toxoplasmosis. Ultrasound assessment of echogenic bowel is usually subjective by comparing the echogenicity with adjacent bone or liver. The diagnosis of fetal echogenic bowel in the second trimester has significant implications for prenatal management. Fetal echogenic bowel should be considered an important marker of placental damage. This finding in the second trimester is strongly associated with adverse pregnancy outcome due to utero-placental insufficiency, particularly in women with elevated maternal serum alpha-fetoprotein concentration due to severe feto-maternal bleeding. This review focuses on the definition and diagnosis of this entity and problems raised by echogenic bowel due to subjectivity of the diagnosis. It also includes the pathophysiology in the different conditions and the prevalence of each condition. Based on this review, we suggest the evaluation that is needed, as well as the recommendations to follow-up, during the remaining term of pregnancy according to the literature.

Moderate to severe thrombocytopenia during pregnancy.

OBJECTIVE: The objective was to investigate obstetric risk factors, complications, and outcomes of pregnancies complicated by moderate to severe thrombocytopenia. MATERIALS AND METHODS: A retrospective case-control study comparing 199 pregnant women with moderate to severe thrombocytopenia (platelet count below 100x10(9)/l) with 201 pregnant women without thrombocytopenia, who delivered between January 2003 to April 2004. Stratified analysis, using the Mantel-Haenszel procedure was performed in order to control for confounders. RESULTS: The main causes of thrombocytopenia were gestational thrombocytopenia (GT) (59.3%), immune thrombocytopenic purpura (ITP) (11.05%), preeclampsia (10.05%), and HELLP (Hemolysis, elevated liver enzymes and low platelet count) syndrome (12.06%). Women with thrombocytopenia were significantly older (30.7+/-5.9 versus 28.7+/-5.7; p=0.001) compared with patients without thrombocytopenia, and had higher rates of labor induction (OR=4.0, 95% CI=2.2-7.6, p<0.001) and preterm deliveries (OR=3.5, 95% CI=1.9-6.5, p<0.001). Even after controlling for labor induction, using the Mantel-Haenszel technique, thrombocytopenia was significantly associated with preterm delivery (weighted OR=3.14, 95% CI=1.7-6.0, p<0.001). Higher rates of placental abruption were found in pregnant women with thrombocytopenia (OR=6.2, 95% CI=1.7-33.2, p=0.001). In a comparison of perinatal outcomes, higher rates of Apgar scores <7 at 5 min were noted in infants of mothers with thrombocytopenia (OR=6.3, 95% CI=1.8-33.8, p=0.001), intrauterine growth restriction (IUGR; OR=4.6, 95% CI=1.5-19.1, p=0.003), and stillbirth (65/1000 versus 0 p<0.001). These adverse perinatal outcomes were found in rare causes of thrombocytopenia such as disseminated intravascular coagulation (DIC), familial thrombotic thrombocytopenic purpura (TTP), anti-phospholipid antibodies (APLA) syndrome, and myeloproliferative disease, and not among patients with GT. CONCLUSIONS: Moderate to severe maternal thrombocytopenia points to a higher degree of severity of the primary disease, which increases perinatal complications. However, the adverse outcome is specifically attributed to preeclampsia, HELLP syndrome, and rare causes, while the perinatal outcome of GT and ITP is basically favorable. Special attention should be given to patients with thrombocytopenia due to preeclampsia, HELLP syndrome, and rarer causes during pregnancy.

Impact of hypnosis during embryo transfer on the outcome of in vitro fertilization-embryo transfer: a case-control study.

OBJECTIVE: To investigate whether hypnosis during ET contributes to successful IVF/ET outcome. DESIGN: Case-control clinical study. SETTING: Academic Fertility and IVF Unit, Soroka Medical Center, Beer-Sheva, Israel. PATIENT(S): Infertile couples undergoing IVF. INTERVENTION(S): Ninety-eight IVF/ET cycles with hypnosis during the ET procedure were matched with 96 regular IVF/ET cycles. MAIN OUTCOME MEASURES: Comparison of clinical pregnancy and implantation rates between the two groups. RESULT(S): We obtained 52 clinical pregnancies out of 98 cycles (53.1%) with an implantation rate of 28% among hypnosis IVF/ET cycles, and 29 out of 96 (30.2%) clinical pregnancies and an implantation rate of 14.4% in the control cycles. Our overall IVF program pregnancy rate for the same period was 32.1%. Logistic regression analysis was performed emphasizing the positive contribution of hypnosis to the IVF/ET conception rates. CONCLUSION(S): This study suggests that the use of hypnosis during ET may significantly improve the IVF/ET cycle outcome in terms of increased implantation and clinical pregnancy rates. Furthermore, it seems that the patients' attitude to the treatment was more favorable.

Cerebral palsy and fetal inflammatory response syndrome: a review.

Cerebral palsy (CP) is the most common cause of severe physical disability in childhood. The precise etiological factor for the development of the majority of cases of CP has not been identified, however, prematurity is considered to be the leading identifiable risk factor. During the last decade, intrauterine infection/inflammation has been identified as the most common cause of preterm delivery and neonatal complications. When microorganisms or their products gain access to the fetus they stimulate the production of cytokines and a systemic response termed FIRS (Fetal Inflammatory Response Syndrome). Subsequently, FIRS was implicated as a cause of fetal or neonatal injury that leads to CP and chronic lung disease. Several authors found an increase in the risk for CP in infants born to mothers with clinical chorioamnionitis, especially in preterm neonates. A relationship between CP and intra-amniotic inflammation was demonstrated, intrauterine infection may lead to activation of the cytokine network which in turn can cause white matter brain damage and preterm delivery, as well as the future development of CP. This white matter insult is identified clinically as periventricular leucomalacia (PVL) which is associated with the subsequent development of impaired neurological outcomes of variable severity including CP.

Placental angiopoietin-1 and angiopoietin-2 expression and correlation with birth weight in twins.

OBJECTIVE: To study the expression of angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2) in human placentas of dizygotic dichorionic twins in relation to fetal growth. STUDY DESIGN: Placentas from dizygotic-dichorionic twins (n=14) obtained from normal uncomplicated pregnancies were collected immediately after delivery. A quantitative assessment of the placental expression of Ang1 and Ang2 was done using quantitative PCR. Birth weight and anthropometric parameters were measured. Statistical analysis was preformed. RESULTS: Ang1 and Ang2 were expressed in the placentas. We found a significant positive correlation between birth weight and expression of both Ang1 and Ang2 (p<0.009, p<0.011, respectively). In addition, there was a significant positive correlation between skin fold, BMI and Ang1 expression (p<0.0001 and p<0.01, respectively). CONCLUSION: A positive correlation between twin birth weight and placental angiogenesis was found. We suggest that placental expression of Ang1 and Ang2 may have an important role in fetal growth in twin pregnancy.

Postpartum infection treatments: a review.

Upper genital tract infections are the most common complications of the puerperium. Less frequent complications are mastitis and septic pelvic thrombophlebitis. Several risk factors including obstetrical, gynaecological, demographic and surgical, are associated with an increased rate of postpartum endometritis and their influence is higher after a caesarean than vaginal delivery. Postpartum endometritis rate range from 15 to 35%. Their identification should be prioritized to prevent this complication. The vaginal flora plays a central role in the development of endometritis. Prophylactic antibiotic treatment at the time of caesarean delivery has helped reduce the rate of postpartum endometritis. When endometritis has been identified and cultures from the genital tract obtained. empirical therapy should be instituted until culture results are available and only then, if needed, therapy changed according to the microorganism's sensitivity. The use of penicillins, cephalosporins, aminoglycosides, metronidazole, macrolides, beta-lactamases inhibitors and quinolones has been reviewed. Various available therapies for endometritis and the experience and results of several authors were analysed. Cost-effectiveness is one of the most important aspects in the decision making process in searching for the best therapy. The monitoring of infection rates within each institution to determine the effectiveness of the prophylactic agent to be used is imperative; it would reduce costs and at the same time, provide the best adequate therapy. After reviewing all the aspects of the different therapies used in case of postpartum endometritis, it may be concluded that the combination of clindamycin and gentamicin is preferred as it can be administered once-daily, and is also the least expensive. Other issues to be taken into account are the number of daily doses and duration of therapy, factors that affect patients compliance and cost of hospitalisation.