Eran Zilberberg

Maternal and neonatal outcomes of large for gestational age pregnancies.

Objective. To compare maternal and neonatal outcomes of term large for gestational age (LGA) pregnancies and adequate for gestational age (AGA) pregnancies. Design. Retrospective analysis. Setting. Large university research medical center. Population. All term singleton LGA (birthweight ≥90th percentile) and AGA pregnancies (birthweight 10.1–89.9th percentile) delivering between 2004 and 2008. Methods. Data collected included maternal age, gestational age at delivery, mode of delivery, birthweight, fetal sex, and maternal and neonatal complications. Birthweight percentiles were determined according to locally derived gender‐specific birthweight tables. Main outcome measures. Comparisons between LGA and AGA pregnancies and between LGA 90–94.9th, 95–98.9th and ≥99th percentile. Results. The study population comprised 34 685 pregnancies; 3900 neonates matched the definition of term LGA. Maternal age and gestational age at delivery were significantly higher for LGA neonates. Significantly more LGA neonates were born by cesarean section, and significantly more LGA pregnancies were complicated by postpartum hemorrhage (PPH), shoulder dystocia or neonatal hypoglycemia, and had a longer hospitalization period. Maternal and neonatal risks increased as birthweight increased from the 90–94.9th to 95–98.9th to ≥99th percentile. Specifically, the risks of shoulder dystocia (odds ratio 2.61, 3.35 and 5.11, respectively), PPH (odds ratio 1.81, 2.12 and 3.92, respectively) and neonatal hypoglycemia (odds ratio 2.53, 3.8 and 5.19, respectively) all increased linearly with birthweight percentile. Conclusions. Large for gestational age pregnancies are associated with an increased rate of cesarean section, PPH, shoulder dystocia and neonatal hypoglycemia, as well as longer hospitalization. These risks increase as the birth percentile rises. These risks need to be emphasized in pre‐delivery counseling.

The aged uterus: multifetal pregnancy outcome after ovum donation in older women

BACKGROUND We aimed to investigate whether multifetal pregnancies are at risk of more pregnancy complications in women of advanced age after ovum donation. METHODS Pregnancy outcome in women after ovum donation aged 40 and above was extracted. Labor and delivery data as well as antenatal records of women carrying twins were compared with those of singletons, as well as to a control group of all twin pregnancies delivered at Sheba Medical Center during 2007. RESULTS One hundred and twenty-five women after ovum donation aged > or = 40 were studied. Of those, 42 women carried twin pregnancies and 83 carried singletons. The 42 women carrying twins comprised the study group and were compared with 417 control women with twins. Mean maternal age was 49.2 +/- 4.3 years. Hypertensive complications (50%), diabetes in pregnancy (31%) and hospitalization in pregnancy (69%) were all extremely high in the study group. Mean gestational age at delivery was lower for the study group compared with controls (35.2 +/- 2.3 versus 35.7 +/- 2.6 weeks), with 35.7% of infants in the study group born < or = 34 weeks gestation compared with 21.8% of controls, (OR: 1.99, 95% CI: 1.02-3.89). Mean birthweight was also significantly lower for study group infants compared with controls, with 77% of study infants born <2500 g compared with only 60% of controls (OR: 2.22, 95% CI: 1.3-3.77). CONCLUSIONS Pregnancy in advanced maternal age women after ovum donation carrying twins is associated with significant maternal and fetal complications, with increased risks of prematurity and lower birthweight. Possibly, the aged uterus is less suitable for carrying a multifetal pregnancy than a younger uterus. Therefore, the alternative of transferring a single, good-quality embryo should be the preferred option.

Maternal and neonatal outcomes of macrosomic pregnancies

Summary Background To compare maternal and neonatal outcomes of term macrosomic and adequate for gestational age (AGA) pregnancies. Material/Methods A retrospective analysis was performed on all term singleton macrosomic (birth weight ≥4000 g) and AGA (birth weight >10th percentile and <4000 g) pregnancies delivered at our hospital between 2004 and 2008. Data collected included maternal age, gestational age at delivery, mode of delivery, birth weight, fetal gender, maternal and neonatal complications. Comparisons were made between macrosomic and AGA pregnancies and between different severities of macrosomia (4000–4250 g, 4250–4500 g and ≥4500 g). Results The study population comprised of 34,685 pregnancies. 2077 neonates had birth weight ≥4000 g. Maternal age and gestational age at delivery were significantly higher for macrosomic neonates. Significantly more macrosomic neonates were born by cesarean section, and were complicated with shoulder dystocia, neonatal hypoglycemia, and had longer hospitalization period (both in vaginal and cesarean deliveries). Specifically, the odds ratio (OR) relative to AGA pregnancies for each macrosomic category (4000–4250 g, 4250–4500 g and ≥4500 g) of shoulder dystocia was 2.37, 2.24, 7.61, respectively, and for neonatal hypoglycemia 4.24, 4.41, 4.15, respectively. The risk of post partum hemorrhage was statistically increased when birth weight was >4500 g (OR=5.23) but not for birth weight between 4000–4500 g. No differences were found in the rates of extensive perineal lacerations between AGA and the different macrosomic groups. Conclusions Macrosomia is associated with increased rate of cesarean section, shoulder dystocia, neonatal hypoglycemia, and longer hospitalization, but not associated with excessive perineal tears. Increased risk of PPH was found in the >4500g group.

Male disadvantage for neonatal complications of term infants, especially in small-for-gestational age neonates

Abstract Objective: Sex differences in long and short-term outcomes for infants are observed. This has also been shown for several neonatal complications in preterm neonates. We aimed to evaluate whether sex impacts neonatal outcome among term neonates. Furthermore, we were interested in whether small-for-gestational age male and female neonates at term presented with different patterns of neonatal complications. Methods: Data on all term singleton deliveries and respective neonatal outcomes between 2004 and 2008 at a single tertiary medical center were utilized for this retrospective cohort study. Immediate neurological complications were defined as one or more of the following: intraventricular hemorrhage, convulsions, asphyxia and acidosis. Neonatal complications were compared between male and female term infants, as well as male and female term small-for-gestational age (SGA) neonates. Results: 37 342 singleton neonates were born ≥37 weeks’ gestation. 19 112 neonates were males. Birth weight, cesarean sections and operative deliveries were significantly higher for males. Neonatal hypoglycemia and immediate neurological complications were significantly more frequent in males. For term SGA’s, low 5-min apgar scores (<7) at 39–40 weeks were 2.65 times higher for males compared with females, as was hypoglycemia. Conclusions: Male infants at term, especially male SGA infants, are more likely to encounter complications during labor and require special neonatal care due to metabolic and/or neurological complications.

Chemerin concentrations in maternal and fetal compartments: implications for metabolic adaptations to normal human pregnancy

Abstract Objectives: Chemerin, a novel adipocytokine, has been implicated in major metabolic and inflammatory processes. Study aims were to determine whether circulating maternal chemerin concentration (1) differs between pregnant and non-pregnant women, (2) changes as a function of gestational age, and (3) correlates with maternal insulin resistance. In addition, we investigated which compartment, maternal, fetal or placental, is the source of chemerin in maternal circulation. Methods: The study included three groups: Non-pregnant (n=18), pregnant women in the first trimester (n=19) and pregnant women in the third trimester (n=33). Chemerin was measured in cord blood and in maternal serum samples taken before and after delivery. Chemerin mRNA expression was evaluated in fetal and human adult tissues. Results: Chemerin serum concentration was significantly higher in pregnant women in the third trimester than in non-pregnant and pregnant women in the first trimester. Chemerin concentration positively correlated with body mass index (BMI) and insulin resistance. Antenatal chemerin concentration was significantly lower than that during the postpartum period. Neonatal chemerin did not correlate with maternal one. Chemerin mRNA expression was abundant in fetal and adult liver and omental fat, but relatively low in placenta. Conclusions: Chemerin is increased during normal gestation and is associated with maternal BMI and insulin resistance. Maternal tissues, possibly liver and adipose tissue, contribute to the increased maternal chemerin concentration.

Is the oocyte quality affected by endometriosis? A review of the literature

Endometriosis is an estrogen-dependent chronic inflammatory condition that affects women in their reproductive period causing infertility and pelvic pain. The disease, especially at the ovarian site has been shown to have a detrimental impact on ovarian physiology. Indeed, sonographic and histologic data tend to support the idea that ovarian follicles of endometriosis patients are decreased in number and more atretic. Moreover, the local intrafollicular environment of patients affected is characterized by alterations of the granulosa cell compartment including reduced P450 aromatase expression and increased intracellular reactive oxygen species generation. However, no comprehensive evaluation of the literature addressing the effect of endometriosis on oocyte quality from both a clinical and a biological perspective has so far been conducted. Based on this systematic review of the literature, oocytes retrieved from women affected by endometriosis are more likely to fail in vitro maturation and to show altered morphology and lower cytoplasmic mitochondrial content compared to women with other causes of infertility. Results from meta-analyses addressing IVF outcomes in women affected would indicate that a reduction in the number of mature oocytes retrieved is associated with endometriosis while a reduction in fertilization rates is more likely to be associated with minimal/mild rather than with moderate/severe disease. However, evidence in this field is still far to be conclusive, especially with regards to the effects of different stages of the disease and to the impact of patients’ previous medical/surgical treatment(s).

Combined Effect of Fetal Sex and Advanced Maternal Age on Pregnancy Outcomes

Background Fetal sex and maternal age are each known to affect outcomes of pregnancies. The objective of the present study was to investigate the influence of the combination of maternal age and fetal sex on pregnancy outcomes in term and post-term singleton pregnancies. Material/Methods This was a retrospective study on term singleton pregnancies delivered between 2004 and 2008 at the Chaim Sheba Medical Center. Data collected included maternal age, fetal sex, and maternal and neonatal complications. The combined effect of fetal sex and maternal age on complications of pregnancy was assessed by multivariable logistic regression models. Results The study population comprised 37,327 pregnancies. The risk of operative deliveries increased with maternal age ≥40 and in pregnancies with male fetuses. The risk of maternal diabetes and of longer hospitalization increased as maternal age increased, and in women <40 carrying male fetuses. The risk of hypertensive disorders increased in pregnancies with males as maternal age advanced. The risk of shoulder dystocia and neonatal respiratory complications increased in male neonates born to women<40. The risk of neonatal hypoglycemia increased in males for all maternal ages. Conclusions Risk assessment for fetal sex and advanced maternal age were given for different pregnancy complications. Knowledge of fetal sex adds value to the risk assessment of pregnancies as maternal age increases.

Do poor-responder patients benefit from increasing the daily gonadotropin dose during controlled ovarian hyperstimulation for IVF?

Abstract We aim to assess the in vitro fertilization-embryo transfer (IVF-ET) outcome in patients receiving an extremely high 450 daily dose (IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF. Moreover, in those who failed to conceive while using 450 daily dose (IU) of gonadotropins, we aim to evaluate whether increasing the daily dose gonadotropins to 600 IU will improve IVF outcome. All consecutive women, admitted to our IVF unit and underwent COH consisting of daily gonadotropin dose of 450 IU were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. Nine-hundred one consecutive IVF cycles were evaluated. While there was no between-group difference in the duration of COH, patients who conceived were significantly younger, yielded higher number of oocytes retrieved and embryos transferred and had significantly lower cancellations. In a sub-analysis, including only those patients who failed to conceive while using 450 daily dose (IU) of gonadotropins, and who underwent a subsequent IVF cycle attempt with the used of 600 IU daily dose of gonadotropins, no improvements in COH characteristics or cancellation rates were observed with increasing the daily gonadotropin dose to 600 IU. To conclude, in poor responders undergoing COH with an extremely high daily gonadotropin dose (450 IU), the most important factors that predict IVF success are female age and the number of oocytes retrieved. Moreover, patients who failed to conceive on a daily gonadotropin dose of 450 IU will not benefit from increasing the dose to 600 IU and should therefore consider the options of egg donation or adoption. Chinese abstract 本研究目的在于评估在控制性卵巢超刺激（COH）阶段每日给予超大剂量促性腺素（450 IU/天）对患者体外受精-胚胎移植（IVF-ET）结果的影响。此外，对于给予促性腺素每日剂量450 IU治疗失败的患者，我们将剂量增至600 IU，评估她们IVF的结局。研究对象为本IVF中心接受COH治疗且每日应用促性腺素剂量为450 IU的患者。评估指标包括卵巢刺激特征、获卵数、胚胎移植数及妊娠率。本研究共纳入了901例连贯的IVF治疗周期。COH阶段无组间差异，治疗成功的患者显著特征为年龄小、获卵数目与胚胎移植数目多且无效胚胎少。进一步研究仅包含应用促性腺素450 IU每日治疗失败，且愿意尝试在接下来的治疗周期中增加促性腺素剂量至600 IU每日的患者，但结果显示增加剂量并未改善COH特征与无效胚胎率。结果表明，卵巢反应性低下的患者在接受每日超大剂量促性腺素（450 IU）COH治疗时，最重要的影响IVF成功的因素是患者年龄与获卵数目。此外，若每日促性腺素剂量为450 IU治疗失败的患者，增加剂量至600 IU并不能使其获益，建议考虑卵子捐赠或领养途径。

Influence of seasonal variation on in vitro fertilization success

Objective To evaluate the influence of seasonal variation on in vitro fertilization (IVF) outcome in a large cohort population. Methods & materials A total of 5,765 IVF cycles conducted in Sheba medical center between 2013 and 2016 were retrospectively analyzed. The treatment cycles included 4214 ovarian stimulation and ovum pick up (OPU) cycles of which 3020 resulted in fresh embryo transfer and 1551 vitrified- warmed cycles of which1400 resulted in warmed embryo transfer. Cycles were assigned to seasons according to the date of OPU for fresh embryo transfer cycles or according to the date of embryo warming for vitrified warmed embryo transfer cycles. Results There were no statistically significant differences between the calendar months or seasons concerning the number of oocytes retrieved or fertilization rate in the fresh cycles. Throughout the 4 years of the study, the monthly clinical pregnancy rate fluctuated between 18.2% and 27.9% per fresh embryo transfer (mean 23.3%) and between 17.7% and 29.4% per vitrified warmed embryo transfer (mean 23%). These fluctuations did not follow any specific seasonal pattern. Conclusions Our study did not demonstrate any significant influence of the calendar months or seasons on the clinical pregnancy rates of fresh or vitrified warmed embryo transfers. It might be speculated that the complete pharmaceutical control of the ovarian and endometrial function, as well as the homogeneous treatments, procedures and laboratory equipment used during the study period have lowered the influence of seasonal effect on IVF treatment outcome.

A novel approach to infertility treatment of advance-age patient with prominent intramural fibroid

Abstract We report for the first time on a case of infertile advance-age patient with large intramural fibroid, who conceived following a course of Ulipristal. The patient underwent two fresh fertility preserving IVF cycles, with cryopreservation of 9 day-3 embryos, followed by a 12 weeks course of Ulipristal (5 mg per day) and a subsequent frozen-thawed embryo transfer with her own previously cryopreserved embryos. We, therefore, believe that Ulipristal is a valuable addition to treatment armamentarium of advance-age infertile patient with prominent intramural fibroid.