Publications by authors named "Raoul Orvieto"

222 Publications

The association between level of physical activity and pregnancy rate after embryo transfer: a prospective study.

Reprod Biomed Online 2021 Jan 28. Epub 2021 Jan 28.

Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Tel-Hashomer, Ramat-Gan 52621, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.

Research Question: Is physical activity after embryo transfer, as assessed by a smart band activity tracker, associated with decreased pregnancy rates?

Design: Prospective observational cohort study comprising infertile women aged < 38 years, who had undergone fewer than three previous embryo transfers, achieved a good ovarian response and were undergoing frozen-thawed embryo transfer in a tertiary-referral centre. A validated smart band activity tracker was used to assess physical activity level immediately after the embryo transfer and until the pregnancy test. No specific recommendations were given to participants on level or intensity of physical activity. Physicians and patients were blinded to the data stored in the pedometer. Primary outcome was ongoing pregnancy rate.

Results: Fifty women met the inclusion criteria. Ongoing pregnancy rate was 30%. In a pooled analysis, participants walked significantly fewer steps per day on the day of embryo transfer compared with the first 2 days after embryo transfer (4075, interquatile range [IQR] 2932-5592 versus 5204, IQR4203-8584, P = 0.01). No significant difference was observed between pregnant women and non-pregnant women in the median steps per day after embryo transfer until serum beta-HCG was measured (7569, IQR 6008-10884 versus 6572.5, IQR 5299-8786, P = 0.43). No significant difference was observed in the median number of steps on the day of embryo transfer or the first 2 days after embryo transfer between pregnant and non-pregnant women.

Conclusions: A quantitative objective assessment of the association between physical activity and pregnancy rates after frozen-thawed embryo transfer was conducted. Ambulation after embryo transfer has no adverse effect on pregnancy rates and, therefore, women should resume regular activity immediately after embryo transfer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2021.01.013DOI Listing
January 2021

Improving Reporting of Clinical Studies Using the POSEIDON Criteria: POSORT Guidelines.

Front Endocrinol (Lausanne) 2021 19;12:587051. Epub 2021 Mar 19.

Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples, Federico II, Naples, Italy.

The POSEIDON (atient-riented trategies ncompassing ndividualizeocyte umber) criteria were developed to help clinicians identify and classify low-prognosis patients undergoing assisted reproductive technology (ART) and provide guidance for possible therapeutic strategies to overcome infertility. Since its introduction, the number of published studies using the POSEIDON criteria has increased steadily. However, a critical analysis of existing evidence indicates inconsistent and incomplete reporting of critical outcomes. Therefore, we developed guidelines to help researchers improve the quality of reporting in studies applying the POSEIDON criteria. We also discuss the advantages of using the POSEIDON criteria in ART clinical studies and elaborate on possible study designs and critical endpoints. Our ultimate goal is to advance the knowledge concerning the clinical use of the POSEIDON criteria to patients, clinicians, and the infertility community.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.587051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017440PMC
March 2021

Biosimilar recombinant follitropin alfa preparations versus the reference product (Gonal-F®) in couples undergoing assisted reproductive technology treatment: a systematic review and meta-analysis.

Reprod Biol Endocrinol 2021 Apr 2;19(1):51. Epub 2021 Apr 2.

Global Medical Affairs Fertility, Research and Development, Merck KGaA, F135/002, Darmstadt, 64293, Germany.

Background: Live birth has increasingly been identified as the standard clinical approach to measure the success of medically assisted reproduction (MAR). However, previous analyses comparing biosimilar preparations of follitropin alfa versus the reference product (GONAL-f®, Merck KGaA, Darmstadt, Germany or GONAL-f® RFF; EMD Serono, Inc., Rockland, MA), have had insufficient power to detect differences in clinically meaningful outcomes such as live birth.

Methods: Medline, Embase, the Cochrane Library, Web of Science and clinical trial registries were searched for randomised controlled trials (RCTs) and conference abstracts comparing biosimilar follitropin alfa versus the reference product in controlled ovarian stimulation (COS) cycles published before 31 October 2020. Only studies in humans and publications in English were included. Retrieved studies were screened independently by two authors based on titles and abstracts, and then by full text.

Inclusion Criteria: RCTs comparing follitropin alfa biosimilar preparations with the reference product in infertile patients of any age, with any type of infertility for any duration, undergoing COS for the purposes of MAR treatment (including frozen cycles). The primary outcome was live birth. Combined data for biosimilar preparations were analysed using a fixed-effects model.

Results: From 292 unique records identified, 17 studies were included in the systematic review, representing five unique RCTs that were included in the meta-analysis. Rates of live birth (RR = 0.83, 95% CI 0.71, 0.97; 4 RCTs, n = 1881, I = 0%), clinical pregnancy (RR = 0.82, 95% CI 0.72, 0.94; 4 RCTs, n = 2222, I = 0%) and ongoing pregnancy (RR = 0.81, 95% CI 0.68, 0.96; 4 RCTs, n = 1232, I = 0%) were significantly lower with biosimilar preparations versus the reference product. Rates of cumulative live birth and cumulative clinical pregnancy were also significantly lower with biosimilars versus the reference product. There was high risk of publication bias.

Conclusions: This meta-analysis included data from RCTs evaluating the efficacy and safety of the biosimilar follitropin alfa preparations and demonstrated lower probability of live birth and pregnancy (ongoing and clinical) in couples treated with biosimilar preparations compared with the reference product. This study provides more insight into the differences between biosimilar r-hFSH preparations and the reference product than previously reported.

Trial Registration: Registration number: CRD42019121992 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12958-021-00727-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017804PMC
April 2021

A Novel Stimulation Protocol for Poor-Responder Patients: Combining the Stop GnRH-ag Protocol with Letrozole Priming and Multiple-Dose GnRH-ant: A Proof of Concept.

Gynecol Obstet Invest 2021 Mar 24:1-6. Epub 2021 Mar 24.

Department of Obstetrics and Gynecology, Infertility and IVF Unit, Chaim Sheba Medical Center, Tel Hashomer, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objective: The objective of this study was to examine whether the combined Stop GnRH-agonist (GnRH-ag), letrozole priming, and multiple-dose GnRH-antagonist (GnRH-ant) protocol may improve in vitro fertilization/intracytoplasmic sperm injection cycle in poor ovarian responders (PORs).

Design: This was a historical cohort, proof of concept study under tertiary setting at University affiliated Medical Center.

Patients: Five PORs fulfilling the POSEIDON Group 4 criteria were included.

Main Outcome Measures: Number of oocytes retrieved, number of top-quality embryos (TQEs), and controlled ovarian hyperstimulation (COH) variables were the main outcome measures.

Results: The combined Stop GnRH-ag, letrozole priming, and multiple-dose GnRH-ant COH protocol revealed significantly higher number of follicles >13 mm on the day of hCG administration and higher number of oocytes retrieved, with non-significantly more TQEs and a reasonable clinical pregnancy rate.

Conclusions: The combined Stop GnRH-ag, letrozole priming, and multiple-dose GnRH-ant COH protocol is a valuable tool in the armamentarium for treating POSEIDON Group 4 patients. Further large prospective studies are needed to elucidate its role in POR and to identify the specific characteristics of women (before initiating ovarian stimulation) that will aid both fertility specialists' counseling and their patients in adjusting the appropriate COH protocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000513669DOI Listing
March 2021

Is there still a rationale for non-invasive PGT-A by analysis of cell-free DNA released by human embryos into culture medium?

Hum Reprod 2021 Mar 4. Epub 2021 Mar 4.

The Center for Human Reproduction, New York, NY, USA.

Human embryos utilise an array of processes to eliminate the very high prevalence of aneuploid cells in early embryo stages. Human embryo self-correction was recently demonstrated by their ability to eliminate/expel abnormal blastomeres as cell debris/fragments. A whole genome amplification study has demonstrated that 63.6% of blastocysts expelled cell debris with abnormal chromosomal rearrangements. Moreover, 55.5% of euploid blastocysts expel aneuploid debris, strongly suggesting that the primary source of cell free DNA in culture media is expelled aneuploid blastomeres and/or their fragments. Such a substantial ability to self-correct downstream from the blastocyststage, therefore, renders any chromosomal diagnosis at the blastocyststage potentially useless, and this, unfortunately, also must particularly include non-invasive PGT-A based on cell-free DNA in spent medium. High rates of false-positive diagnoses of human embryos often lead to non-use and/or disposal of embryos with entirely normal pregnancy potential. Before adopting yet another round of unvalidated PGT-A as a routine adjunct to IVF, we here present facts that deserve to be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humrep/deab042DOI Listing
March 2021

Cleavage vs blastocyst stage embryos: how are they interrelating?

Arch Gynecol Obstet 2021 Feb 23. Epub 2021 Feb 23.

IVF Unit, Department of Obstetrics and Gynecology, Sackler Faculty of Medicine, Chaim Sheba Medical Center, Tel-Hashomer, Tel Aviv University, Tel Aviv, Israel.

Purpose: To assess the variables that may predict which cleavage-stage embryo may develop into a blastocyst, and vice versa, to determine whether the cleavage-stage embryo morphology should be taken into consideration when transferring the embryo at the blastocyst stage.

Methods: A single center, retrospective cohort study. The study cohort included 3072 patients undergoing 3607 retrieval cycles and 23,124 embryos at the cleavage stage. We assessed the blastulation rate and evaluated which variables impact the ongoing pregnancy rate.

Results: High blastulation rate correlates with higher embryos' grading (I > II > III > IV > V) and higher number of blastomeres (8 > 7 > 6 > 5 > 4). 949 patients had fresh single blastocyst transfers. The ongoing pregnancy rate was 28.9% per transfer. Patients with ongoing pregnancies were significantly younger (34.3 vs. 36 years, p < 0.001), had higher number of oocyte yield (9.8 vs. 9, p = 0.02), and an increased rate of good-quality embryos transferred (70.7% vs. 47.7%, p = 0.001). When evaluating embryos progression, we found that whenever embryo developed to a good-quality blastocyst, its appearance at the cleavage stage did not affect ongoing pregnancy rate.

Conclusion: Higher the number of blastomeres and better embryo grading were found to correlate with a higher blastulation rate. Nevertheless, if the embryo has already developed to a top-quality blastocyst, its morphology at the cleavage stage did not impact ongoing pregnancy rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00404-021-06003-zDOI Listing
February 2021

Cognitive achievements in school-age children born following assisted reproductive technology treatments: A prospective study.

Early Hum Dev 2021 Apr 4;155:105327. Epub 2021 Feb 4.

Women & Children's Health Research Unit, Gertner Institute for Epidemiology & Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel; School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Background: While assisted reproductive technology is increasingly prevalent, there is concern amid conflicting findings reported regarding the long-term outcomes of children born following these treatments. The aim of this research was to investigate aspects of cognitive development in early school-age Israeli children born following assisted reproductive technology (ART) treatments, compared to those spontaneously conceived (SC).

Method: This prospective follow-up study was based on an Israeli cohort recruited from June 2006 to December 2008, that included 561 women whose pregnancies were achieved by ART treatments and 600 women whose pregnancies were SC. When the children were 7-8 years old, 759 of their mothers were interviewed by telephone, and 294 were came for developmental assessment. The examination included: Kaufman Brief Intelligence Test; Kaufman Assessment Battery for Children (arithmetic only); Test of Everyday Attention for Children; Beery-Buktenica Developmental Test of Visual-Motor Integration and Supplemental Test for Visual Perception; Rey-Osterrieth Complex Figure Test; Aleph-ad-Tav Hebrew reading and writing; Tavor Picture Naming Expressive Vocabulary Test. Multivariable analyses were adjusted for maternal years of education (≤12, 13+) at child's birth and child's sex.

Results: Cognitive function, visual-motor ability, attention, and verbal skills of children born after ART treatments were similar to those of SC children, upon both univariate and multivariable analysis.

Conclusion And Implications: No significant differences were found between the ART and SC groups on any of the measures examined. This finding offers couples seeking ART treatments improved information regarding child development during the important and formative school years.

What This Paper Adds: Increasing rates of ART treatments arouse concern about long-term outcomes for offspring, and conflicting findings have been reported with respect to the skills necessary to their academic success. This prospective follow-up study compared school-age children born following ART with spontaneously-conceived children. Children were examined by developmental psychologists, and cognitive function, visual-motor, attention, verbal, and performance skills were similar in both groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.earlhumdev.2021.105327DOI Listing
April 2021

Commentary on two recently published formal guidelines on management of "mosaic" embryos after preimplantation genetic testing for aneuploidy (PGT-A).

Reprod Biol Endocrinol 2021 Feb 18;19(1):23. Epub 2021 Feb 18.

The Fertility Clinic, Ringhospital, University Hospital of Copenhagen, Copenhagen, Denmark.

Two professional societies recently published opinions on the clinical management of "mosaic" results from preimplantation genetic testing for aneuploidy (PGT-A) in human blastocyst-stage embryos in associations with in vitro fertilization (IVF). We here point out three principal shortcomings: (i) Though a most recent societal opinion states that it should not be understood as an endorsement of the use of PGT-A, any discussion of how PGT-A should be clinically interpreted for all practical purposes does offer such an endorsement. (ii) The same guideline derived much of its opinion from a preceding guidance in favor of utilization of PGT-A that did not follow even minimal professional requirements for establishment of practice guidelines. (iii) Published guidelines on so-called "mosaic" embryos from both societies contradict basic biological characteristics of human preimplantation-stage embryos. They, furthermore, are clinically unvalidated and interpret results of a test, increasingly seen as harmful to IVF outcomes for many infertile women. Qualified professional organizations, therefore, should finally offer transparent guidelines about the utilization of PGT-A in association with IVF in general.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12958-021-00716-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890905PMC
February 2021

Pregnancy and neonatal outcomes of twin pregnancies - the role of maternal age.

J Perinat Med 2021 Feb 17. Epub 2021 Feb 17.

The Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Ramat-Gan, Israel.

Objectives: We aim to study the association of maternal age with maternal and neonatal complications in twin pregnancies.

Methods: A retrospective cohort study of dichorionic-diamniotic twin pregnancies stratified into three groups according to maternal age ("A" <25, "B" 25-34 and "C" 35-44 years old). Outcome measures included pregnancy, delivery and neonatal complications. A sub-analysis of fertilization pregnancies only was conducted.

Results: Compared with younger women (groups A [n=65] and B [n=783]), older women [group C (n=392)] demonstrated significantly higher rates of gestational diabetes mellitus (B 6.6% vs. A 0%, p =0.027, C 10.2% vs. B 6.6%, p =0.032), were more likely to undergo cesarean deliveries (C 66.6%, B 57.6%, A 52.3%, p =0.007), and were at increased risk of having more than 20% difference in weight between the twins (C 24.5%, B 17.4%, A 16.9%, p =0.013). Other outcomes, including preeclampsia, did not differ between the groups. A sub-analysis of the fertilization only pregnancies was performed. Compared with younger women (groups A [n=18] and B [n=388]), older women (group C [n=230]) underwent more cesarean deliveries (p=0.004), and had more than 20% difference in weight between the twins (p<0.004). Other outcomes, including gestational diabetes mellitus rates and preeclampsia, did not differ between the groups.

Conclusions: Women at advanced maternal age with dichorionic twin pregnancies had significantly higher rates of gestational diabetes mellitus, cesarean deliveries and fetal weight discordancy as compared with younger women. In contrast, the incidence of preeclampsia was not affected by maternal age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpm-2020-0386DOI Listing
February 2021

Future fertility of patients with zero oocytes yield in their first IVF cycle attempt.

PLoS One 2021 16;16(2):e0246889. Epub 2021 Feb 16.

Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), Ramat Gan, Israel.

Purpose: We aim to estimate the future fertility of patient undergoing their first IVF cycle attempt with no oocyte retrieved, and to identify factors that might predict those who will conceive in subsequent IVF cycle attempt.

Methods: A cohort retrospective study of all consecutive women attending our IVF unit, for their first IVF cycle attempt, between January 2013 to December 2019, who reached the ovum pick-up (OPU) stage with zero oocyte retrieved. Patients' characteristics and infertility-treatment-related variables in the first IVF cycle attempt were compared between those who conceived in a subsequent cycle and those who did not. Moreover, infertility-treatment-related variables during successful cycles resulting in pregnancy were compared to those without.

Results: 59 met the study inclusion criteria, yielding zero oocytes. During the follow-up period, 12 (20.3%) women conceived (one conceived twice), and 8 (14%) gave birth to a live infant. Cumulative live-birth rate per OPU and per patients were 4% and 14%, respectively. Clinical pregnancies were achieved after 3.61+1.4 cycle attempts (range: 1-6), with no live-births following the fifth IVF cycle attempt. No in-between group differences were observed in ovarian stimulation variables of their first IVF cycle attempt. Moreover, in those cycles resulting in pregnancy, patients achieved a significantly higher number of fertilized oocytes (2.15+1.5 vs 0.94+1.5, respectively; p<0.01) and a higher mean top-quality embryos (TQE) (1.76+0.9 vs 0.73+1.2, respectively; p<0.003).

Conclusion: Women yielding zero oocytes at their first IVF cycle attempt, may achieve 14% cumulative live-birth rate after 5 IVF cycle attempts. Moreover, those who conceived in subsequent IVF cycle attempts were those achieving 2 or more fertilized oocytes/TQE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246889PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886146PMC
February 2021

Is There Any Association Between the Number of Oocytes Retrieved, Women Age, and Embryo Development?

Reprod Sci 2020 Nov 25. Epub 2020 Nov 25.

Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel.

While most studies focused on the association between the number of oocytes retrieved and LBR, there is lack of analysis highlighting the effect of the number of oocyte retrieved on top quality embryo (TQE) rate in different age groups. We aimed to study the correlations between the number and ratio of TQE, as assessed by morphology only, according to the number of oocytes retrieved, and to evaluate the impact of patients' age. This was a retrospective study that includes 1639 patients who underwent 2263 IVF cycles between 2016 and 2019. Patients were categorized into four groups according to the number of oocytes retrieved: 1-3, 4-9, 10-14, or > 15 oocytes (OPU groups A-D, respectively). Another classification was according to patient's age < 35, 35-40, and > 40 years. Morphologically, TQE (both cleavage stage and blastocyst) was defined as those eligible for transfer or vitrification. TQE was assessed both as a fraction of oocytes retrieved per patients (rate) and the average TQE per number oocytes retrieved category. For all age subgroups, a negative significant association was observed between the number of oocytes retrieved and TQE rate (56.1%, 43.6%, 35.9%, and 34.3% for groups A-D, respectively). The reduction was significant up to 14 oocytes retrieved and plateau thereafter. On the other hand, TQE rate was significantly increased as women age increased, from 36.1% TQE rate in young women (< 35 years) to 40.3% for 35-40 years to 42.5% in older patients (> 40 years). Finally, a linear regression revealed a drop in TQE rate of - 0.5% for every oocyte retrieved, while an increased in TQE rate of + 0.7%, as the women age increased by 1 year. While young women are able to recruit more oocyte, including medium/low quality, older women recruit less oocytes, with good quality, as demonstrated by their higher morphologically TQE rate relative to the number of oocyte retrieved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-020-00391-4DOI Listing
November 2020

Placenta accreta spectrum in subsequent pregnancy following myomectomy.

J Matern Fetal Neonatal Med 2020 Nov 25:1-8. Epub 2020 Nov 25.

Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Israel.

Purpose: To compare the prevalence of placental abnormalities in pregnancy following different modes of operative myomectomy.

Methods: A retrospective cohort study, including all women after myomectomy that gave birth in a single tertiary care center from February 2011 to January 2019. Data was collected from the patients' medical files and completed by telephone questionnaire. Patients were stratified to 3 groups, according to the mode of operative myomectomy (laparotomy, laparoscopy, hysteroscopy). Groups were compared for women demographics, fibroid's characteristics, operative management, post-operative placental evaluation and delivery characteristics. Primary outcome was defined as the need for any intervention for placental separation during the third phase of the delivery.

Results: Two hundred forty one women met inclusion criteria. Complete follow-up was achieved in 199 (82.57%) women, of whom 82, 89, and 28 underwent laparoscopic, laparotomy and hysteroscopic myomectomy, respectively. There were no in-between groups differences in women's age, BMI, and gravidity. Disruption of the endometrial cavity during laparoscopy and laparotomy was reported in 3 (3.6%) and 7 (7.8%) cases, respectively ( = .21). During the subsequent pregnancy following myomectomy, placenta accreta spectrum disorder was suspected in only one woman in each of the study groups ( = .63). Placenta previa was low and comparable between groups. Vaginal delivery rate was significantly higher in the hysteroscopy group, as compared to the laparoscopy or the laparotomy groups [11 (36.3%) vs. 5 (6.1%) vs. 4 (4.5%);  = .001], with significantly lower need for manual lysis of the placenta [11(39.0%) vs. 51 (62.1%) vs. 62 (69.7%);  = .01] and further interventions for blood loss control.

Conclusions: Subsequent pregnancy following surgical myomectomy was not found to be associated with higher prevalence placental abnormality. Furthermore, other than manual lysis, the different modes of myomectomy did not necessitate any further intervention for complications associated with abnormal placentation requiring intervention.

Key Message: Subsequent pregnancy following surgical myomectomy is not associated with higher prevalence of placental abnormality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2020.1849114DOI Listing
November 2020

How Are They Doing? Neurodevelopmental Outcomes at School Age of Children Born Following Assisted Reproductive Treatments.

J Child Neurol 2021 Mar 2;36(4):262-271. Epub 2020 Nov 2.

Gertner Institute for Epidemiology & Health Policy Research Ltd, Women & Children's Health Research Unit, Tel Hashomer, Israel.

Objective: The purpose of this study was to assess major neurodevelopmental aspects of children conceived by assisted reproductive treatments compared to spontaneously conceived children during the early school years.

Material & Methods: In this follow-up study, mothers of 358 children born following assisted reproductive treatments and 401 spontaneously-conceived children were interviewed by telephone regarding their children's health and development, when the children were 7-8 years old. The main outcomes were maternal responses to 4 questionnaires: Developmental Coordination Disorder Questionnaire, Short Sensory Profile, Autism Spectrum Screening Questionnaire, and the Attention-deficit hyperactive disorder (ADHD) Child Symptom Inventory-4 subscale. Mothers reported diagnoses of ADHD and autism spectrum disorder.

Results: No significant differences were found between the groups in Developmental Coordination Disorder Questionnaire or Short Sensory Profile scores upon univariate or multivariable analyses. There was a slightly higher but nonsignificant rate of diagnosed ADHD among children in the assisted reproductive treatment group (9.6% vs 5.5%; = .18); on multivariable analysis, a nonsignificant increase in ADHD was also found for assisted reproductive treatment children (hazard ratio 1.45, 95% confidence interval 0.81-2.61). Regarding the Child Symptom Inventory-4 criteria for ADHD among the children who had never been diagnosed, there was also a slightly higher but nonsignificant rate among the assisted reproductive treatments compared to spontaneously-conceived children on univariate (2.4% vs 1.8%; = .50) and multivariable analysis (odds ratio 0.88, 95% confidence interval 0.27-2.86). Autism spectrum disorder diagnosis or Autism Spectrum Screening Questionnaire scores were not significantly different; however, 5 of the 6 children with autism spectrum disorder diagnoses were in the assisted reproductive treatment group.

Conclusions: Neurodevelopmental measures were similar in both groups, although nonconclusive regarding ADHD and autism spectrum disorder risk. These findings contribute to the knowledge regarding long-term assisted reproductive treatment outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0883073820967169DOI Listing
March 2021

The role of ICSI vs. conventional IVF for patients with advanced maternal age-a randomized controlled trial.

J Assist Reprod Genet 2021 Jan 28;38(1):95-100. Epub 2020 Oct 28.

IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, 52620, Tel-Hashomer, Israel.

Objectives: This study aimed to evaluate the role of intracytoplasmic sperm injection (ICSI) in the treatment of non-male factor infertile patients aged ≥ 39.

Methods: This is a single-center, prospective, randomized controlled clinical trial, between March 2018 and December 2019. Sixty-nine patients were recruited, and sixty patients participated in the study. Their ovaries were randomized prior to the beginning of the ovarian stimulation: the oocytes from one side (n = 257) were allocated to the ICSI (ICSI arm), while those of the contralateral side (n = 258) were allocated to conventional insemination (IVF arm). The fertilization rate per oocyte retrieved, number of zygotes (2PN), and cleavage-stage embryos were assessed and compared between the two study groups.

Results: The average number of zygotes (3.1 vs. 2.7 p = 0.45), the fertilization rate (72.4% vs. 65.1% p = 0.38), the average number of cleavage-stage (2.8 vs. 2.4 p = 0.29), and the average top-quality embryos (TQE) cleavage-stage embryos (1.7 vs. 1.6 p = 0.94) were comparable between the two groups. The TQE rate per randomized oocyte (41.2% vs. 41% p = 0.8) was also similar in both groups.

Conclusions: ICSI does not improve the reproductive outcomes of advanced-age patients undergoing conventional insemination for non-male factor infertility.

Trial Registration: NCT03370068.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10815-020-01990-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822989PMC
January 2021

Testicular sperm retrieval: What should we expect from the fresh and subsequent cryopreserved sperm injection?

Andrologia 2021 Feb 18;53(1):e13849. Epub 2020 Oct 18.

Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), Ramat Gan, Israel.

We sought to compare ICSI outcomes of cycle using fresh versus thawed TESE spermatozoa obtained during the previous fresh TESE. All consecutive couples undergoing ICSI cycles using fresh TESE spermatozoa, followed by ICSI cycle using cryopreserved sperm remaining from the previous fresh TESE procedure were included. Ovarian stimulation (OS)/laboratory variables and cycle outcome were assessed and compared between those utilising fresh versus thawed TESE spermatozoa. Seventy-five couples were evaluated, with no in-between groups differences in OS nor embryological variables. While implantation and LBR per embryo transfer were nonsignificantly higher in the frozen as compared to the fresh TESE, there was a trend towards higher LBRs per patient in the frozen TESE group. The cumulative miscarriage rate (4% versus 14.7%, p < .022 respectively) was significantly lower and the cumulative LBR (34.7% versus 16%, p < .007 respectively) was significantly higher using frozen TESE spermatozoa. Moreover, significantly higher proportion of frozen TESE sperm samples used pentoxifylline to enhance sperm motility. In conclusion, the results of ICSI cycles using frozen TESE spermatozoa are as good, or even better than using fresh TESE spermatozoa. Further studies are required to explore the factors responsible for the improved ICSI outcome, while using frozen versus fresh TESE sperm samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/and.13849DOI Listing
February 2021

Does the number of embryos loaded on a single cryo-carrier affect post-vitrification survival rate?

Zygote 2021 Feb 13;29(1):87-91. Epub 2020 Oct 13.

Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: We aimed to assess whether the survival rate of embryos is influenced by the number of embryos/oocytes loaded on a single cryo-carrier during vitrification.

Methods: This was a retrospective study that included 974 patients who underwent thawing of 1896 embryo-warming cycles between September 2016 and January 2020. A distinct analysis was made for cleavage stage embryos (2-10-cell stage) and blastocysts. For vitrification, embryos were placed in a Cryotop™ open device using a SAGE vitrification kit following the manufacturer's instructions. Warming was carried using a SAGE warming vitrification kit according the manufacturer's instructions.

Results: Total post-vitrification survival rates of embryos at the cleavage stage or blastocyst stage was 94.8%. At the cleavage stage, cryo-preserving three embryos per single cryo-carrier gave the highest full intact embryo survival rate (91.5%) compared with one or two embryo(s) per single cryo-carrier (85.7%, P < 0.0002 and 87.3%, P < 0.004). Conversely, post warmed full intact blastocyst survival rate for two blastocysts was significantly lower compared with one blastocyst (76.7% vs. 87.9%, P < 0.0193) per single cryo-carrier.

Conclusion: Post-thawing survival rate following vitrification is affected by the number of embryos per single cryo-carrier undergoing the vitrification equilibration phase, with the optimum number of three cleaved embryos or one blastocyst per single cryo-carrier. Further studies are required to determine the optimum number of cleaved embryos or blastocysts that should be loaded onto a single cryo-carrier vitrification device.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0967199420000453DOI Listing
February 2021

Do human embryos have the ability of self-correction?

Reprod Biol Endocrinol 2020 Oct 6;18(1):98. Epub 2020 Oct 6.

Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), 56261, Ramat Gan, Israel.

Human embryogenesis frequently coinciding with cell division mistakes contributing to pervasive embryonic aneuploidy/mosaicism. While embryo self-correction was elegantly demonstrated in mouse models, human studies are lacking. Here we are witness to human embryos ability to eliminate/expel abnormal blastomeres as cell debris/fragments. Each blastocyst and its corresponding debris were separated and underwent whole genome amplification. Seven of the 11 pairs of blastocysts and their corresponding cell debris/fragments revealed discordant results. Of the 9 euploid blastocysts, four showed euploid debris, while in the others, the debris were aneuploid. In the remaining pairs, the debris showed additional aneuploidy to those presented by their corresponding blastocyst. The observed ability of human embryos to self-correction doubts many invasive and non-invasive preimplantation testing for aneuploidy at the blastocyst stage, rendering high rate of false positive (discarding "good" embryos) by identifying the cell-free DNA originated from the expelled cell debris, as aneuploidy/mosaic blastocyst.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12958-020-00650-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539487PMC
October 2020

Reply: Dual versus hCG trigger for final follicular maturation.

Hum Reprod 2020 11;35(11):2636

Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), Ramat Gan, Israel.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humrep/deaa215DOI Listing
November 2020

The Effect of Ovarian Stimulation on Endothelial Function-A Prospective Cohort Study using Peripheral Artery Tonometry.

J Clin Endocrinol Metab 2020 12;105(12)

Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

Context: Gonadotropin-releasing hormone agonist (GnRH-a) serves as an alternative to human chorionic gonadotropin (hCG) to trigger final oocyte maturation, while it significantly reduces the risk of ovarian hyperstimulation syndrome (OHSS), probably by attenuating vascular/endothelial activation.

Objectives: The objectives of this work are to compare the effect of different modes of final follicular maturation (hCG vs GnRH-a) following ovarian stimulation (OS) for in vitro fertilization (IVF) on endothelial function.

Design And Setting: A prospective cohort study was conducted at a tertiary medical center.

Participants: Patients age 37 years or younger, undergoing OS for IVF, were allocated into 2 groups according to the type of final follicle maturation: the hCG group (n = 7) or the GnRH-a group (n = 8).

Intervention: Endothelial function was assessed by measurement of the peripheral arterial tonometry in reaction to temporary ischemia at 3 study points: day 3 of menstrual cycle (day 0), day of hCG/GnRH-a administration (day trigger) and day of oocyte pick-up (day OPU). The ratio of arterial tonometry readings before and after ischemia is called the reactive hyperemia index (RHI). Decreased RHI (< 1.67) indicates endothelial dysfunction.

Main Outcome Measures: The main outcomes measures of this study included endothelial function at 3 study points during OS with different modes of triggering final follicular maturation.

Results: The mean RHI values at day 0 were within the normal range for all patients and comparable between both groups (hCG: 1.7 ± 0.3 vs GnRH-a: 1.79 ± 0.4, P = .6). All patients presented a decrease in RHI values on day trigger, which did not differ between the 2 groups (1.62 ± 0.3 vs 1.4 ± 0.2, respectively, P = .2). However, the hCG group demonstrated a further decrease in RHI on day OPU, whereas patients who received GnRH-a had restored normal endothelial function reflected by increased RHI values (1.4 ± 0.2 vs 1.75 ± 0.2, respectively, P = .03).

Conclusions: Triggering final follicular maturation with GnRH-a restored normal endothelial function, whereas hCG trigger resulted in a decrease in endothelial function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa681DOI Listing
December 2020

Does a Large (>24 mm) Follicle Yield a Competent Oocyte/Embryo?

Gynecol Obstet Invest 2020 23;85(5):416-419. Epub 2020 Sep 23.

Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Israel,

Aim: To evaluate the effect of large follicular size (≥24 mm) at day of oocyte retrieval on oocyte/embryo quality.

Patients And Methods: A cohort study was conducted in a single tertiary medical center between July 2018 and May 2019. Before ultrasound-guided follicular aspiration, follicles were measured and divided into 2 groups according to their maximal dimensional size: large: ≥24 mm and normal: <24 mm. Microscopic examination of the follicular aspirates was performed by an embryologist. Each follicle aspirated was evaluated for oocyte maturation, oocyte fertilization, and embryo quality.

Results: 428 follicles were measured, including 383 (62.81%) in the normal and 45 (14.06%) in the large follicle groups. Oocytes were achieved during aspiration from 297 (75.5%) and 29 (64.4%) of the normal and large follicle groups, respectively (p = 0.05). No in-between group differences were observed in mature oocyte (MII), fertilization, and top-quality embryo (TQE) rates. Nevertheless, once a zygote (2PN) was achieved, a trend toward a higher TQE rate/2PN was found in the large follicle group (16/19 [84.2%] vs. 115/171 [67.3%]; p = 0.062).

Conclusion: While a nonsignificant decrease in oocyte recovery rate was found in follicles ≥24 mm, the zygote and TQE per follicle were comparable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000510876DOI Listing
April 2021

The reproducibility of trophectoderm biopsies - The chaos behind preimplantation genetic testing for aneuploidy.

Authors:
Raoul Orvieto

Eur J Obstet Gynecol Reprod Biol 2020 Nov 14;254:57-58. Epub 2020 Sep 14.

Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), Ramat Gan, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Tarnesby-Tarnowski Chair for Family Planning and Fertility Regulation, at the Sackler Faculty of Medicine, Tel-Aviv University, Israel. Electronic address:

Chromosomal mosaicism is a common feature of early human embryos development. "Mosaic" embryos display very low rates of concordance between multiple trophectoderm biopsies and between multiple trophectoderm and inner cell mass biopsies using next-generation sequencing. The here presented data clearly demonstrate the limitations and shortages of the preimplantation genetic testing for aneuploidy screening test, which are not in alignment with WHO basic requirements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.07.052DOI Listing
November 2020

Obstetric and Perinatal Outcomes in Pregnancies Conceived After Preimplantation Genetic Testing for Monogenetic Diseases.

Obstet Gynecol 2020 10;136(4):782-791

Department of Obstetrics and Gynecology and the Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer; The Sackler School of Medicine and the Tarnesby-Tarnowski Chair for Family Planning and Fertility Regulation, Tel Aviv University, Tel Aviv, Israel.

Objective: To investigate whether the addition of embryo biopsy performed during preimplantation genetic testing for monogenic diseases is associated with a higher risk of obstetric and neonatal complications compared with in vitro fertilization (IVF) without preimplantation genetic testing or spontaneously conceived pregnancies.

Methods: This is a cohort study of all pregnancies conceived after preimplantation genetic testing for monogenic diseases (PGT-M group) from 2006 to 2018 at Sheba Medical Center, Israel. The control groups included patients who had conceived spontaneously (spontaneous conception group) or by IVF without preimplantation genetic testing (IVF group) and delivered at Sheba Medical Center. The obstetrics outcomes were compared among the groups. Multivariable regression modeling was performed, focusing on the relationship between preimplantation genetic testing and adverse outcomes.

Results: Final analysis included 345 singleton and 76 twin deliveries in the PGT-M group. The spontaneous conception group included 5,290 singleton and 92 twin deliveries. The IVF group included 422 singleton and 101 twin deliveries. Among singleton pregnancies, patients in the PGT-M group had a higher rate of hypertensive disorders (6.9%) compared with those in the spontaneous conception group (2.3%; odds ratio [OR] 3.3; 95% CI 1.9-4.8; adjusted odds ratio [aOR] 14.8; 95% CI 7.4-29.8) and the IVF group (4.7%; OR 1.5; 95% CI 0.8-2.7; aOR 5.9; 95% CI 1.9-18.2). Likewise, patients in the PGT-M group had a higher rate of small-for-gestational age neonates (12.4%) compared with those in the spontaneous conception group (3.9%; OR 3.4; 95% CI 2.4-4.9; aOR 2.3; 95% CI 1.5-3.4) and the IVF group (4.5%; OR 3; 95% CI 1.7-5.2; aOR 2.5; 95% CI 1.7-5.2). Among twin pregnancies, patients in the PGT-M group also had an increased rate of hypertensive disorders compared with those in the spontaneous conception group (4.3%; OR 4.1; 95% CI 1.2-13.3; aOR 10.9; 95% CI 2.3-50) and the IVF group (4%; OR 4.5; 95% CI 1.4-14.7; aOR 3.7; 95% CI 1.1-12.8).

Conclusion: Pregnancies conceived after preimplantation genetic testing for monogenic disorders were associated with an increased risk of obstetric complications compared with pregnancies conceived spontaneously or by IVF without preimplantation genetic testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/AOG.0000000000004062DOI Listing
October 2020

Is Day-4 morula biopsy a feasible alternative for preimplantation genetic testing?

PLoS One 2020 11;15(9):e0238599. Epub 2020 Sep 11.

Department of Obstetrics and Gynecology, Sheba Medical Center, Ramat-Gan, Israel.

Objective: To assess the efficacy and clinical outcome of PGT-M undertaken on Day-3, Day-4 and Day-4 "delayed" embryos that were unsuitable for biopsy on Day-3.

Design And Setting: Cohort-historical study of all consecutive patients admitted to the IVF-PGT-M program in a large tertiary center.

Main Outcome Measure(s): The pregnancy rates and the percentages of complete, incomplete diagnosis, PCR failure, abnormal embryos in PGT of Day-3 cleavage-stage, Day-4 and Day-4 "delayed" embryos.

Patients And Methods: We reviewed the medical files of all consecutive patients admitted to our IVF for a fresh IVF-PGT-M cycle. Patients were divided into 3 groups according to the day of blastomere biopsy: Day 3 cleavage-stage, Day-4 morula and Day-4 "delayed" embryos. The laboratory data, genetic diagnostic and clinical results were collected and compared between the different study groups.

Results: Nine hundred and six patients underwent PGT-M cycles in our PGT program: 747, 127 and 32 in the Day-3, Day- 4 and Day-4 "delayed" groups, respectively. Ongoing pregnancy rates per transfer and per patient (15.8% and 9.4%, respectively) were non-significantly lower in the Day-4 "delayed", compared to Day-3 (21.4% and 17.5%, respectively) and Day-4 (24.3% and 19.7%, respectively). When comparing ALL morulas (Day-4 and Day-4 "delayed") to ALL cleavage-stage embryos (Day-3, Day-4 and Day-4 "delayed"), a significantly higher ongoing pregnancy rate was demonstrated following the transfer of embryos derived from morula biopsy, as compared to biopsy at the cleavage-stage (33.3% vs 20.5%, p<0.03, respectively).

Conclusion: Day-4 embryo biopsy is feasible and yields comparable and even higher ongoing pregnancy rate if undertaken at the morula stage. Further studies evaluating the cumulative live-birth rate per started cycles in Day-3 vs Day-4 embryo biopsy for PGT-M are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238599PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486131PMC
October 2020

Can Oocyte Diameter Predict Embryo Quality?

Reprod Sci 2021 Mar 2;28(3):904-908. Epub 2020 Sep 2.

TRIO Fertility Partners, Division of Reproductive Sciences, University of Toronto, 655 Bay St 11th floor, Toronto, ON, M5G 2K4, Canada.

With the recent increased utilization of oocyte vitrification for the purpose of fertility preservation, information regarding the future fertility potential of the frozen oocytes is mandatory. Nowadays, there is a relative lack of data about prediction of assisted reproductive technique (ART) success relying on the retrieved oocytes. In the present study, we therefore aimed to investigate whether oocyte diameter might predict the quality of the developing embryo. A retrospective, single-center cohort study. Oocytes retrieved following controlled ovarian hyperstimulation cycles during 2016 and incubated in a time-lapse incubator system were analyzed. Oocytes were grouped by mean oocyte diameter (MOD) and incubated for 5 days before the final morphological evaluation done by an expert embryologist. A total of 471 cycles which yielded 3355 metaphase II oocytes were included in the analysis. Embryos developed from oocytes with MOD close to the average (Average 1SD < MOD < Average + 1SD) had increased good-quality blastulation rates compared with embryos that developed from very small or very large oocytes. Oocytes with MOD between 105.96 and 118.69 μm have better probability of becoming top-quality D5 blastocysts (17.1-17.4% grade 1 embryos). There is a correlation between oocyte's MOD and the embryo quality at day 5. The oocytes with near average MOD have a better chance to develop to a good-quality embryo. Therefore, the study suggests that MOD might serve as a predictor for embryo grading at day 5.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-020-00306-3DOI Listing
March 2021

Does the time interval between the diagnosis to hysteroscopic evacuation of retained products of conception affect reproductive outcome?

Arch Gynecol Obstet 2020 12 12;302(6):1523-1528. Epub 2020 Aug 12.

Department of Obstetrics and Gynecology, Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel.

Background: Retained products of conception (RPOC) refer to the presence of placental and/or fetal tissue in the uterus following delivery, miscarriage, or termination of pregnancy. The presence of such tissue might lead to complications, which might be the culprit of secondary infertility. Although some studies have considered the management of symptomatic RPOC, there are no data regarding the management of asymptomatic, incidentally diagnosed RPOC, nor the optimal time for surgical intervention required to prevent adverse reproductive outcomes.

Objective: This study aimed to examine whether the time interval between the pregnancy termination to surgical evacuation of RPOC influences the reproductive outcome in asymptomatic women.

Design: This is a retrospective cohort study, which includes women who were admitted for an elective procedure in the gynecology day-care clinic due to suspected RPOC. The diagnosis was made during patients' routine examination following either delivery or miscarriage between the years 2010 and 2018.

Setting: Records of women who were admitted to the day-care gynecology department during the years 2010-2018 for hysteroscopic removal of RPOC.

Patients: The patients were divided into three groups, according to the time from desired pregnancy to conception following the procedure (> 6; 3-6 and < 3 months). Data regarding obstetric history prior to the procedure was retrieved from patients' clinical files, while data concerning reproductive outcome following the procedure was obtained by telephone questionnaires.

Intervention: Data regarding obstetric history prior to the procedure was retrieved from patients' clinical files, while data concerning reproductive outcome following the procedure was obtained by telephone questionnaires.

Measurements: 75 patients whose reproductive outcome could be analyzed were included in the study. The time interval between the end of pregnancy and surgical intervention was analyzed as a continuous variable and was compared between the three groups, together with parameters such as age and obstetric history.

Results: There were no significant differences between the groups.

Conclusions: The main finding of the present study is that the time interval between the end of pregnancy and surgical evacuation of the asymptomatic, incidentally diagnosed RPOC, has no significant implication on patients' reproductive outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00404-020-05711-2DOI Listing
December 2020

Machine learning vs. classic statistics for the prediction of IVF outcomes.

J Assist Reprod Genet 2020 Oct 11;37(10):2405-2412. Epub 2020 Aug 11.

Department of Obstetrics and Gynecology, Sheba Medical Center, 52561, Ramat Gan, Israel.

Purpose: To assess whether machine learning methods provide advantage over classic statistical modeling for the prediction of IVF outcomes.

Methods: The study population consisted of 136 women undergoing a fresh IVF cycle from January 2014 to August 2016 at a tertiary, university-affiliated medical center. We tested the ability of two machine learning algorithms, support vector machine (SVM) and artificial neural network (NN), vs. classic statistics (logistic regression) to predict IVF outcomes (number of oocytes retrieved, mature oocytes, top-quality embryos, positive beta-hCG, clinical pregnancies, and live births) based on age and BMI, with or without clinical data.

Results: Machine learning algorithms (SVM and NN) based on age, BMI, and clinical features yielded better performances in predicting number of oocytes retrieved, mature oocytes, fertilized oocytes, top-quality embryos, positive beta-hCG, clinical pregnancies, and live births, compared with logistic regression models. While accuracies were 0.69 to 0.9 and 0.45 to 0.77 for NN and SVM, respectively, they were 0.34 to 0.74 using logistic regression models.

Conclusions: Our findings suggest that machine learning algorithms based on age, BMI, and clinical data have an advantage over logistic regression for the prediction of IVF outcomes and therefore can assist fertility specialists' counselling and their patients in adjusting the appropriate treatment strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10815-020-01908-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550518PMC
October 2020

Timing day-3 vitrification for PGT-M embryos: pre- or post-blastomere biopsy?

J Assist Reprod Genet 2020 Oct 8;37(10):2413-2418. Epub 2020 Aug 8.

Department of Obstetrics and Gynecology, Infertility and IVF Unit, Sheba Medical Center, Ramat Gan, Israel.

Purpose: To assess the efficacy and clinical outcomes of preimplantation genetic testing for monogenic diseases (PGT-M), following blastomere biopsy prior or following vitrification.

Methods: A cohort-historical study of all consecutive patients admitted to IVF in a large tertiary center for PGT-M and PCR cycle from September 2016 to March 2020. Patients were divided into 4 groups: Group A1 consisted of patients undergoing day-3 embryos biopsy followed by a fresh transfer of unaffected embryos. Group A2 consisted of Group A1 patients that their surplus unaffected embryos were vitrified, thawed, and transferred in a subsequent FET cycle. Group B1 consisted of patients that their day-3 embryos were vitrified intact (without biopsy) for a subsequent FET cycle. Later embryos were thawed and underwent blastomere biopsies, and the unaffected embryos were transferred, while the surplus unaffected embryos were re-vitrified for a subsequent FET cycle. Group B2 consisted of Group B1 patients that their surplus unaffected embryos were re-vitrified, thawed, and transferred in a subsequent FET cycle. The laboratory data and clinical results were collected and compared between groups.

Results: A total of 368 patients underwent 529 PGT-M cycles in our center: 347 with day-3 embryos biopsied before undergoing vitrification (Group A1) and 182 following vitrification and thawing (Group B1). There were no between group differences in embryo survival rate post-thawing, nor the ongoing implantation and pregnancy rates.

Conclusion: In PGT-M cycles, the timing of embryos vitrification, whether prior or following blastomere biopsy, has no detrimental effect on post-thawing embryo survival rate, nor their potential ongoing implantation and pregnancy rates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10815-020-01914-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550449PMC
October 2020

Stop GnRH-Agonist Combined with Multiple-Dose GnRH-Antagonist for Patients with Elevated Peak Serum Progesterone Levels Undergoing Ovarian Stimulation for IVF: A Proof of Concept.

Gynecol Obstet Invest 2020 24;85(4):357-361. Epub 2020 Jun 24.

Infertility and IVF Unit, Department of Obstetrics and Gynecology, Tel Aviv University, Tel Aviv, Israel.

Aim: The aim of the study was to examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may overcome progesterone elevation during the late follicular phase.

Patients And Methods: A cohort historical, proof of concept study consisting of 11 patients with progesterone elevation (>3.1 nmol/L) during conventional IVF/intracytoplasmic sperm injection (ICSI), who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist ovarian stimulation (OS) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle.

Results: The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly lower peak progesterone levels, with significantly higher numbers of follicles >13 mm in diameter on the day of hCG administration, oocytes retrieved, mature oocytes, and top-quality embryos, with an acceptable clinical pregnancy rate (18.2%).

Conclusions: The combined Stop GnRH-ag/GnRH-ant OS protocol is a valuable tool in the armamentarium for treating patients with progesterone elevation during the late follicular phase. Further large prospective studies are needed to validate our observation and to characterize the appropriate patients' subgroup, which might benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000508875DOI Listing
February 2021

Do fertility treatments affect labor induction success rate? A retrospective cohort study.

J Matern Fetal Neonatal Med 2020 Jun 17:1-5. Epub 2020 Jun 17.

Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.

To evaluate labor induction success rate by Foley catheter (FC) on patients who conceived spontaneously, as compared to those who underwent fertility treatments. This retrospective cohort study included all pregnant women hospitalized at a single tertiary care center between January 2011 and May 2018 for induction of labor with FC. The study groups included patients with a singleton pregnancy who conceived after fertility treatments: controlled ovarian hyperstimulation (COH) or fertilization (IVF), while control group included patients who conceived spontaneously. Our primary outcome was the rate of cesarean deliveries. Regression analysis was conducted on the following parameters: age, gravidity, parity, the gestational week, and IVF. The study groups included 59, 321, and 3159 patients who conceived following COH, IVF, or spontaneously, respectively. While 72.1% of patients who conceived spontaneously had a vaginal delivery, only 62.7% and 58% of patients who conceived by COH and IVF had successful labor induction (respectively,  < .01). Similarly, significantly higher cesarean section (CS) rates were demonstrated by patients who conceived by COH and IVF (28.8% and 30%, respectively), compared to the control group (18.7%,  < .01). Regression analysis demonstrated that although age, parity, and the gestational week were significantly related to cesarean sections, no statistically significant association was found regarding fertility treatments ( = .050). The possible association between fertility treatments and cesarean delivery remains an important dilemma for obstetricians and fertility experts. While unadjusted analysis demonstrated such association among patients who undergo labor induction by FC, adjusted analysis has not supported that finding. Further studies focusing on the causes of failed vaginal delivery are needed to further expand our knowledge and to improve patient consultation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2020.1779693DOI Listing
June 2020

Stop GnRH-Agonist Combined With Multiple-Dose GnRH-Antagonist Protocol for Patients With "Genuine" Poor Response Undergoing Controlled Ovarian Hyperstimulation for IVF.

Front Endocrinol (Lausanne) 2020 22;11:182. Epub 2020 May 22.

Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

To examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may improve conventional IVF/intracytoplasmic sperm injection (ICSI) cycle in poor ovarian response (POR) patients. Cohort historical, proof of concept study. Tertiary, University affiliated Medical Center. Thirty POR patients, defined according to the Bologna criteria, who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle, were included. For the purposes of this study, we eliminated a bias in this selection by including only "genuine" poor responder patients, defined as those who yielded up to 3 oocytes following COH with a minimal gonadotropin daily dose of 300 IU. Number of oocytes retrieved, number of top-quality embryos, COH variables. The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly higher numbers of follicles >13 mm on the day of hCG administration, higher numbers of oocytes retrieved, and top-quality embryos (TQE) with an acceptable clinical pregnancy rate (16.6%). Moreover, as expected, patients undergoing the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol required significantly higher doses and a longer duration of gonadotropins stimulation. The combined Stop GnRH-ag/GnRH-ant COH protocol is a valuable tool in the armamentarium for treating "genuine" poor ovarian responders. Further, large prospective studies are needed to elucidate its role in POR and to characterize the appropriate patients subgroup (before initiating ovarian stimulation) that may benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.00182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258857PMC
March 2021