Lena Sagi-Dain

Effect of paternal age on reproductive outcomes in oocyte donation model: a systematic review

OBJECTIVE To perform a meta-analysis of the literature examining the influence of paternal age on oocyte donation outcomes. DESIGN Systematic review of the literature with no language or time restrictions. SETTING Not applicable. PATIENT(S) None. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Pregnancy and live-birth rates. RESULT(S) By independent screening of titles and abstracts, two investigators selected original studies examining the influence of paternal age on oocyte donation outcomes. Twelve articles were included, encompassing a total of 12,538 oocyte-donation cases. No statistically significant correlation was found by most studies between advanced paternal age and the rate of fertilization, cleavage embryo development, implantation, pregnancy, miscarriage, or live birth. A statistically significant decrease in blastocyst embryo formation was suggested in two articles. Except for volume and possibly motility, other sperm characteristics such as concentration and morphology did not alter with age. However, the overall quality of the evidence was rated as very low according to Grading of Recommendations Assessment, Development, and Evaluation criteria. CONCLUSION(S) The available evidence suggests that advancing paternal age is not associated with adverse oocyte donation outcomes, including pregnancy and live-birth rates. However, the suboptimal quality of the available evidence necessitates high-quality, well-adjusted prospective trials that are also aimed at evaluating additional outcomes such as congenital anomalies and various specific long-term disorders.

The role of episiotomy in prevention and management of shoulder dystocia: a systematic review

Importance Shoulder dystocia is an obstetric emergency with potential catastrophic outcomes. Objective To perform a systematic literature review examining the effectiveness of episiotomy in the prevention and management of shoulder dystocia during vaginal birth. Evidence Acquisition Search was conducted by a research librarian in MEDLINE, Web of Science, Cochrane Library, and SCOPUS databases using the terms “episiotomy” and “shoulder dystocia,” with no language or time restrictions. Two investigators independently selected original researches examining the effects of episiotomy on shoulder dystocia and its neonatal and maternal outcomes. Relevant articles were accessed in full text, including manual search of the references. We contacted authors of studies with insufficient or unclear data. Because of clinical and methodological diversity of the studies, meta-analysis was not performed. Results Fourteen articles met the inclusion criteria, encompassing a total of 9769 shoulder dystocia cases. Only 1 study effectively evaluated the role of episiotomy in shoulder dystocia prevention, yielding a nonsignificant result. Three articles assessed neonatal consequences of shoulder dystocia, one of them linking episiotomy to higher risk of neonatal injury. Two of the 3 studies evaluating maternal outcomes showed that episiotomy is related to increased risk of advanced perineal tears. Overall quality of evidence was rated as very low. Conclusions and Relevance Our systematic review found no evidence supporting the use of episiotomy in the prevention and management of shoulder dystocia. This observation carries major clinical and legal implications for the obstetricians. Higher-quality studies are needed to evaluate this important issue. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completion of this educational activity, the reader will be better able to analyze the paucity of existing literature examining the role of episiotomy in the prevention and management of shoulder dystocia, discuss the crucial issues in exploring the subject including uniform definition of shoulder dystocia and the report of episiotomy timing, and assess the knowledge needed to determine whether to perform episiotomy in deliveries with increased risk of shoulder dystocia, such as in cases of macrosomic fetus.

CA 19-9 in evaluation of adnexal mass: retrospective cohort analysis and review of the literature

Objective The aim of this study was to estimate the diagnostic accuracy of serum marker CA 19-9 levels in the triage of adnexal masses. Methods This retrospective cohort study was carried out in patients referred to the Gynecology Department at Carmel Medical Center due to adnexal masses. All patients underwent preoperative measurements of serum CA 125 and CA 19-9 and surgery with histopathologically confirmed diagnosis. Results Between January 2005 and December 2012, 503 patients with adnexal masses were evaluated with serum tumor markers. Combination of CA 19-9 with CA 125, compared with CA 125 levels alone, suggested a nonsignificant effect on sensitivity (86.9% vs. 88.9%, respectively, p = 0.54) or specificity (79.5% vs. 73.5%, p = 0.1) in differentiating malignant from benign adnexal masses. CA 19-9 was not helpful in detecting mucinous histological types or borderline tumors. Mean CA 19-9 levels were higher in metastatic cases compared with primary ovarian malignancy (488.7 ± 1,457 vs. 46.3 ± 149.8 U/mL, respectively, p = 0.001). In mature cystic teratomas, mean CA 19-9 levels were higher and CA 125 levels were lower than in ovarian carcinoma (p = 0.049 and p = 0.0012, respectively). Conclusions The combination of the tumor markers CA 19-9 and CA 125 did not contribute significantly to the detection of malignant adnexal masses compared with CA 125 alone. As our results suggest that higher CA 19-9 levels could be helpful in differentiating metastatic tumors from primary ovarian malignancy; this issue should be investigated in large well-designed prospective cohort trials.

The Effect of Paternal Age on Oocyte Donation Outcomes.

Importance In recent decades, a trend toward delayed childbearing is noted in developed countries. Whereas the effects of maternal age on fertility, pregnancy complications, and postnatal outcomes have been thoroughly explored, consequences of advanced paternal age are less well known. Oocyte donation cycles can be used as an optimal model to analyze the association between male ageing and reproductive outcomes with minimal confounding. Objective The purpose of this work was to summarize the updated and relevant literature dealing with the effect of paternal age on oocyte donation outcomes. Results According to the available evidence from oocyte donation cycles, it seems that no significant association exists between advanced paternal age and fertility. However, this evidence is based on few studies, many of which are of low quality, yielding conflicting results. In addition, the emerging evidence clearly indicates an increased risk of adverse postnatal manifestations of pregnancies conceived by older fathers, including de novo autosomal dominant disorders, impaired neurocognitive development, and increased risk of malignancy. Conclusions and Relevance This review may be of aid to medical practitioners in counseling couples on the risks of delayed childbearing. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this activity, the learner should be better able to analyze the paucity of existing literature examining the effect of paternal age on oocyte donation outcomes, understand the mechanisms underlying the increased risk for postnatal disorders associated with advanced male age, and counsel couples on the risks of delayed childbearing.

The effect of ozonated sterile saline irrigation on the endometrium – A preliminary study

The objective of this study was to evaluate the effect of sterile ozonated saline endometrial irrigation on sonographic and histological endometrial parameters. This prospective investigation was performed in 12 healthy, ovulating women over three consecutive menstrual cycles: control cycle (endometrial irrigation with 10 cc of normal saline at day 10), no intervention cycle and study cycle (irrigation with 10 cc of sterile ozonated saline at day 10). Endometrial thickness was measured by transvaginal ultrasound at days 10 and 12 of the control and study cycles, and endometrial samplings were obtained from the participants two days after the irrigations (i.e. on day 12) for histological evaluation. Ozonated saline irrigation, compared to normal saline irrigation, resulted in a statistically significant elevation of the columnar epithelial height (30.30 ± 3.04 vs. 25.82 ± 3.28 μm, p < 0.003), increased number of endometrial blood vessels (30.48 ± 11.38 vs. 19.12 ± 8.74, p < 0.005) and increased number of stromal cells (191.30 ± 34.40 vs. 151.29 ± 29.98, p < 0.01). In conclusion, sterile ozonated saline irrigation of the endometrium has a significant favourable effect on various histological endometrial parameters. Further studies are needed to evaluate the effect of these changes on endometrial receptivity and pregnancy rates.

Microarray analysis in pregnancies with isolated unilateral kidney agenesis

BackgroundThe objective of our study was to examine the risk for submicroscopic chromosomal aberrations among fetuses with apparently isolated solitary kidney.MethodsData acquisition was performed retrospectively by searching Israeli Ministry of Health-computerized database. All cases having chromosomal microarray analysis (CMA), referred because of an indication of isolated unilateral kidney agenesis between January 2013 and September 2016, were included. Rate of clinically significant CMA findings in these pregnancies was compared to pregnancies with normal ultrasound, based on a systematic review encompassing 9,792 cases and local data of 5,541 pregnancies undergoing CMA because of maternal request.ResultsOf the 81 pregnancies with isolated solitary kidney, 2 (2.47%) loss-of-copy number variants compatible with well-described deletion syndromes were reported (16p11.2–16p12.2 and 22q11.21 microdeletion syndromes). In addition, one variant of unknown significance was demonstrated. The relative risk for pathogenic CMA findings among pregnancies with isolated unilateral renal agenesis was not significantly different compared with the control population.ConclusionCMA analysis in pregnancies with unilateral renal agenesis might still be useful, to the same degree as it can be in the general population.

Effect of Paternal Age on Reproductive Outcomes: Data from Intracytoplasmic Sperm Injection and Oocyte Donation

In recent decades, a prominent tendency for delayed childbearing has been increasingly noted. This trend can be explained by several factors, including prolonged life expectancy, common contraception use, and changing female roles across society. Unfortunately, the phenomenon of advanced parental age has its drawbacks, as it might unintentionally increase the risk of various adverse reproductive and postnatal outcomes. This chapter explores these issues and summarizes current data on the impact of paternal age on reproductive outcomes with ICSI.

Whole-exome sequencing reveals a novel missense mutation in the MARS gene related to a rare Charcot-Marie-Tooth neuropathy type 2U

Charcot‐Marie‐Tooth (CMT) is a heterogeneous group of progressive disorders, characterized by chronic motor and sensory polyneuropathy. This hereditary disorder is related to numerous genes and varying inheritance patterns. Thus, many patients do not reach a final genetic diagnosis. We describe a 13‐year‐old girl presenting with progressive bilateral leg weakness and gait instability. Extensive laboratory studies and spinal magnetic resonance imaging scan were normal. Nerve conduction studies revealed severe lower limb peripheral neuropathy with prominent demyelinative component. Following presumptive diagnosis of chronic inflammatory demyelinating polyneuropathy, the patient received treatment with steroids and intravenous immunoglobulins courses for several months, with no apparent improvement. Whole‐exome sequencing revealed a novel heterozygous c.2209C>T (p.Arg737Trp) mutation in the MARS gene (OMIM 156560). This gene has recently been related to CMT type 2U. In‐silico prediction programs classified this mutation as a probable cause for protein malfunction. Allele frequency data reported this variant in 0.003% of representative Caucasian population. Family segregation analysis study revealed that the patient had inherited the variant from her 60‐years old mother, reported as healthy. Neurologic examination of the mother demonstrated decreased tendon reflexes, while nerve conduction studies were consistent with demyelinative and axonal sensory‐motor polyneuropathy. Our report highlights the importance of next‐generation sequencing approach to facilitate the proper molecular diagnosis of highly heterogeneous neurologic disorders. Amongst other numerous benefits, this approach might prevent unnecessary diagnostic testing and potentially harmful medical treatment.

Prenatal microarray analysis in right aortic arch—a retrospective cohort study and review of the literature

Objective:To examine the risk for clinically significant chromosomal microarray analysis (CMA) findings in fetal right aortic arch (RAA).Methods:Data from all CMA analyses performed owing to isolated RAA reported to the Israeli Ministry of Health between January 2013 and September 2016 were evaluated retrospectively. Risk for abnormal CMA findings was compared with two control populations, based on both previously described 9272 pregnancies with normal ultrasound, and on a local cohort of 5541 pregnancies undergoing CMA testing owing to maternal request. In addition, Pubmed database search was conducted for original researches examining this issue.Results:Of 94 CMA analyses performed owing to isolated RAA, six (6.4%) pathogenic findings were detected (47,XX + 21; 45,X; two 22q11.2 microdeletions; 10p15.3 microdeletion and 16p11.2 duplication). Compared with control groups, an isolated RAA yielded a significantly increased relative risk for abnormal CMA results. Literature search yielded two additional retrospective studies describing microarray testing in RAA and encompassing 57 cases. The overall risk for clinically significant CMA findings was 6.62% (10/151).Conclusions:CMA testing is indicated in cases of prenatal isolated RAA, even in the era of advanced sonographic equipment, routine biochemical screening for Down syndrome and available non-invasive prenatal testing.

Chromosomal microarray findings in pregnancies with an isolated pelvic kidney

Abstract Objective To examine the risk for abnormal chromosomal microarray analysis (CMA) results among fetuses with an apparently isolated pelvic kidney. Methods Data from all CMA analyses performed due to an isolated pelvic kidney reported to the Israeli Ministry of Health between January 2013 and September 2016 were retrospectively obtained. Risk estimation was performed comparing the rate of abnormal observed CMA findings to the general population risk, based on a systematic review encompassing 9272 cases and on local data of 5541 cases. Results Of 120 pregnancies with an isolated pelvic kidney, two gain-of-copy number variants suggesting microduplication syndromes were demonstrated (1.67%). In addition, three variants of unknown significance were detected (2.5%). Conclusion The risk for clinically significant CMA findings among pregnancies with an isolated single pelvic kidney was not significantly different compared to both control populations. The results of our study question the practice of routine CMA analysis in fetuses with an isolated pelvic kidney.