scholarly journals Relationship between follicular volume and oocyte competence, blastocyst development and live-birth rate: optimal follicle size for oocyte retrieval

2018 ◽  
Vol 51 (1) ◽  
pp. 118-125 ◽  
Author(s):  
B. Wirleitner ◽  
J. Okhowat ◽  
L. Vištejnová ◽  
M. Králíčková ◽  
M. Karlíková ◽  
...  
BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e042395
Author(s):  
Simone Cornelisse ◽  
Liliana Ramos ◽  
Brigitte Arends ◽  
Janneke J Brink-van der Vlugt ◽  
Jan Peter de Bruin ◽  
...  

IntroductionIn vitro fertilisation (IVF) has evolved as an intervention of choice to help couples with infertility to conceive. In the last decade, a strategy change in the day of embryo transfer has been developed. Many IVF centres choose nowadays to transfer at later stages of embryo development, for example, transferring embryos at blastocyst stage instead of cleavage stage. However, it still is not known which embryo transfer policy in IVF is more efficient in terms of cumulative live birth rate (cLBR), following a fresh and the subsequent frozen–thawed transfers after one oocyte retrieval. Furthermore, studies reporting on obstetric and neonatal outcomes from both transfer policies are limited.Methods and analysisWe have set up a multicentre randomised superiority trial in the Netherlands, named the Three or Fivetrial. We plan to include 1200 women with an indication for IVF with at least four embryos available on day 2 after the oocyte retrieval. Women are randomly allocated to either (1) control group: embryo transfer on day 3 and cryopreservation of supernumerary good-quality embryos on day 3 or 4, or (2) intervention group: embryo transfer on day 5 and cryopreservation of supernumerary good-quality embryos on day 5 or 6. The primary outcome is the cLBR per oocyte retrieval. Secondary outcomes include LBR following fresh transfer, multiple pregnancy rate and time until pregnancy leading a live birth. We will also assess the obstetric and neonatal outcomes, costs and patients’ treatment burden.Ethics and disseminationThe study protocol has been approved by the Central Committee on Research involving Human Subjects in the Netherlands in June 2018 (CCMO NL 64060.000.18). The results of this trial will be submitted for publication in international peer-reviewed and in open access journals.Trial registration numberNetherlands Trial Register (NL 6857).


Author(s):  
Maria Angeles Roque Fernandez ◽  
Cristina Alvarez Lleo ◽  
Esteban Gonzalez Mirasol ◽  
Maria Resta Serra ◽  
Carmen Garcia Garrido ◽  
...  

2020 ◽  
Vol 35 (7) ◽  
pp. 1630-1636 ◽  
Author(s):  
Phillip A Romanski ◽  
Pietro Bortoletto ◽  
Zev Rosenwaks ◽  
Glenn L Schattman

Abstract STUDY QUESTION Will a delay in initiating IVF treatment affect pregnancy outcomes in infertile women with diminished ovarian reserve? SUMMARY ANSWER A delay in IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation. WHAT IS KNOWN ALREADY In clinical practice, treatment delays can occur due to medical, logistical or financial reasons. Over a period of years, a gradual decline in ovarian reserve occurs which can result in declining outcomes in response to IVF treatment over time. There is disagreement among reproductive endocrinologists about whether delaying IVF treatment for a few months can negatively affect patient outcomes. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of infertile patients in an academic hospital setting with diminished ovarian reserve who started an IVF cycle within 180 days of their initial consultation and underwent an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Diminished ovarian reserve was defined as an anti-Müllerian hormone (AMH) <1.1 ng/ml. In total, 1790 patients met inclusion criteria (1115 immediate and 675 delayed treatment). Each patient had one included cycle and no subsequent data from additional frozen embryo transfer cycles were included. Since all cycle outcomes evaluated were from fresh embryo transfers, no genetically tested embryos were included. Patients were grouped by whether their cycle started 1–90 days after presentation (immediate) or 91–180 days (delayed). The primary outcome was live birth (≥24 weeks of gestation). A subgroup analysis of more severe forms of diminished ovarian reserve was performed to evaluate outcomes for patients with an AMH <0.5 and for patients >40 years old with an AMH <1.1 ng/ml (Bologna criteria for diminished ovarian reserve). Logistic regression analysis, adjusted a priori for patient age, was used to estimate the odds ratio (OR) with a 95% CI. All pregnancy outcomes were additionally adjusted for the number of embryos transferred. MAIN RESULTS AND THE ROLE OF CHANCE The mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85–1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH <0.5 ng/ml (immediate: 18.8%; delayed: 19.1%; OR 0.99, 95% CI 0.65–1.51) and in patients >40 years old with an AMH <1.1 ng/ml (immediate: 12.3%; delayed: 14.7%; OR 1.21, 95% CI 0.77–1.91). LIMITATIONS, REASONS FOR CAUTION There is the potential for selection bias with regard to the patients who started their IVF cycle within 90 days compared to 91–180 days after initial consultation. In addition, we did not include patients who were seen for initial evaluation but did not progress to IVF treatment with oocyte retrieval; therefore, our results should only be applied to patients with diminished ovarian reserve who complete an IVF cycle. Finally, since we excluded patients who started their IVF cycle greater than 180 days from their first visit, it is not known how such a delay in treatment affects pregnancy outcomes in IVF cycles. WIDER IMPLICATIONS OF THE FINDINGS A delay in initiating IVF treatment in patients with diminished ovarian reserve up to 180 days from the initial visit does not affect pregnancy outcomes. This observation remains true for patients who are in the high-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistic or financial reasons, treatment outcomes will not be affected. STUDY FUNDING/COMPETING INTEREST(S) No financial support, funding or services were obtained for this study. The authors do not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER Not applicable.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Vo. Wolff ◽  
I Magaton ◽  
O Stalder ◽  
D Surbek ◽  
P Stute ◽  
...  

Abstract Study question What is the best follicle size, estradiol (E2) serum concentration and endometrial thickness to trigger ovulation in natural cycles? Summary answer Optimal follicles size is 18–22mm but estrogen concentration also need to be considered to maximize oocyte maturity and to minimize premature LH surge. What is known already Timing of the ovulation triggering is essential in infertility treatments based on natural menstrual cycles such as optimized vaginal intercourse, intrauterine inseminations and thawing cycles without hormone replacement therapy. Common parameters to define the day of ovulation triggering are the follicle size and the estrogen concentration. However, data on follicle size and estrogen concentration are either derived from longitudinal evaluations of few ideal participants, are not very detailed or were studied in stimulated cycles. The model of Natural Cycle IVF (NC-IVF) which provides more detailed information has never been used to study this issue. Study design, size, duration Retrospective cross sectional analysis of monofollicular NC-IVF cycles. Follicle size, E2 and LH serum concentrations and endometrial thickness were evaluated on day –5 to 0 (day 0 = day of aspiration). Ovulation was triggered with 5.000IE HCG 36h before aspiration if follicle size was 14–22mm. Patients with irregular cycles, endometriosis >II°, cycles with azoospermia or cryptozoospermia and with inconsistent data were excluded. 606 cycles from 290 women were analysed from 2016 to 2019. Participants/materials, setting, methods Mean age of women undergoing NC-IVF was 35.8±4.0y, median 36y [IQ-range: 34;39]. Each woman performed mean 2.1±1.4, median: 2 [IQ-range: 1–3] NC-IVF cycles at an university based IVF center. All parameters were analysed inter and intraindividually and associations were adjusted for maturity of oocyte, zygote development rate, embryo score, implantation rate and live birth rate. Associations were adjusted for age, cause of infertility and number of previous transfers. Main results and the role of chance Follicle size, E2 concentration and endometrial thickness increased constantly over time. The increase was computed for each cycle without considering any correlation intra patient, revealing an increase of follicle size by 1.04±0.64mm, an increase of E2 concentration by 167.3±76.8pmol/L and endometrial thickness by 0.69±0.59mm per day. Based on a multivariate adjusted model with follicle size, E2 and their interaction, number of retrieved oocytes was associated with E2 concentration (aOR 1.80, 95% CI 1.05–3.11; p = 0.034). Maturity of oocytes was associated not only with E2 concentration (aOR 1.84, 95% CI 1.15–2.94; p = 0.010) but also with follicle size (aOR 1.24, 95% CI 1.01–1.53; p = 0.037) and so was also the interaction of both parameters (aOR 0.96, 95% CI 0.94–0.99; p = 0.017). LH surge was calculated to start in 25% of cases at an E2 level of 545 pmol/l, in 50% of cases at 907pmol/l and in 75% of cases at an E2 level of 1531pmol/l. Live birth rate in cycles with follicles size 14–17 mm was 2.2–3.5% per initiated cycle and in cycles with follicle size 18–22mm 8.5–12.5%. Limitations, reasons for caution Cross sectional studies provides less precise information than longitudinal studies. Follicle size and endometrial thickness were evaluated by several physicians possibly causing some imprecision. Wider implications of the findings: There is a trend towards natural treatment cycles. The study contribute to an optimisation of infertility treatments involving natural cycles. The study gives guidance about the number of days required after a follicle monitoring to reach the optimal time for triggering ovulation. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Marques ◽  
P Rodrigues ◽  
J Aibar ◽  
M J Carvalho ◽  
C E Plancha

Abstract Study question Which are the main factors on first oocyte retrievals influencing the time to achieve a live birth? Summary answer The number of oocytes collected on the first retrieval is the most important factor to decrease time to live birth. What is known already The goal of infertile couples when they attend a fertility clinic is to obtain a healthy baby as soon as possible. Cumulative live birth rate is today considered the most reliable estimate of ART success. However, the time used to achieve such goal is still not clear both to health professionals and patients. Although there is a general idea of which factors predict ART success, both clinicians and embryologists are still not aware of which variables can effectively influence the time to a live birth. Study design, size, duration We analyzed retrospectively 333 couples who performed their first fresh IVF/ICSI cycles from January 2015 to December 2018, along with their eventual subsequent FET and/or IVF/ICSI cycles, leading to 146 live births. The aim of this study was to use “Time” as an additional measure of ART success, and to identify which variable of the first oocyte retrieval has a major influence on time to live birth. Participants/materials, setting, methods We included in total 430 oocyte retrievals and 147 FET cycles. Oocyte donation cycles were excluded. Data were studied cumulatively until the childbirth (couples at risk) or until the last treatment record (censored couples). Cox Regression Model for survival analysis was used to study the variables that may influence the time to live birth, in order to take both confounding and collinearity into account. Main results and the role of chance We considered the date of the first oocyte retrieval as the starting point and the date of the first childbirth as the ending point to determine the time to live birth. The mean age of the woman at the first oocyte retrieval was 36.8±4.67, the cumulative pregnancy rate 43.5% (95%CI:41.77%;45.23%) and the live birth rate 34.0%(95%CI:32.32%;35.63%). As variables for the Cox Regression Model we selected the woman’s age and number of collected oocytes from the first oocyte retrieval. We also considered the number of frozen embryo transfers (FET). We have found a positive association between the number of oocytes collected at the first oocyte retrieval and the period until obtaining a healthy singleton (HR = 1.20;95%CI:1.105–1.297;p>0.001). Conversely, a negative association concerning the number of FET and time to live birth (HR = 0.32;95%CI:0.18–0.562;p>0.001) was demonstrated. Importantly, woman’s age, was not found to have a significant effect on time to live birth. Our results indicated that the number of oocytes collected at the first cycle, but not woman’s age, mostly affect time to live birth. Poor prognosis patients were found to be associated with several embryo transfers. Limitations, reasons for caution This is a retrospective study with a small number of cycles and freeze-all procedures were not included. Additional inclusion of freeze-all procedures in a larger study will be needed to confirm our preliminary results. Wider implications of the findings: This study identified oocyte number at first collection as a major influence on time to live birth. Increased attention to the “Time” parameter will be helpful for health professionals and patients, to further personalize reproductive treatment procedures, potentially decreasing psychological burdens associated with ART treatments. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Esiso ◽  
F Lai ◽  
D Cunningham ◽  
D Garcia ◽  
B Barrett ◽  
...  

Abstract Study question Does rapid or delayed insemination after egg retrieval affect fertilization, blastocyst development and live birth rates in CI and ICSI cycles? Summary answer When performing CI or ICSI <1.5h and >6.5h after retrieval, detrimental effects are moderate on fertilization but do not impact blastocyst usage and birth rates. What is known already Several studies have shown that CIor ICSI performed between 3 to 5 h after oocyte retrieval has improved laboratory outcomes. However, some studies indicate that insemination of oocytes, by either CI or ICSI, within 2 hours or more than 8 hours after oocyte retrieval has a detrimental effect on the reproductive outcome. With some ART centres experiencing an increase in workload, respecting these exact time intervals is frequently challenging. Study design, size, duration A single-center retrospective cohort analysis was performed on 6559 patients (9575 retrievals and insemination cycles) between January 1st2017 to July 31st2019. The main outcome measures were live-birth rates. Secondary outcomes included analysis of fertilization per all oocytes retrieved, blastocyst utilization, clinical pregnancy, and miscarriage rates. All analyses used time of insemination categorized in both CI and ICSI cycles. Fertilization rates across categories was analyzed by ANOVA and pregnancy outcomes compared using Chi-square tests. Participants/materials, setting, methods As part of laboratory protocol, oocyte retrieval was performed 36 h post-trigger. Cycles involving injection with testicular/epidydimal sperm, donor or frozen oocytes were excluded. The time interval between oocyte retrieval and insemination was analyzed in eight categories: 0 (0- <0.5h), 1 (0.5-<1.5h), 2 (1.5-<2.5h), 3 (2.5-<3.5h), 4 (3.5-<4.5), 5 (4.5-<5.5), 6 (5.5-<6.5) and 7 (6.5-<8h). The number of retrievals in each group (0–7) was 586, 1594, 1644, 1796, 1836, 1351, 641 and 127 respectively. Main results and the role of chance This study had a mean patient age of 36.0 years and mean of 12.2 oocytes per retrieval in each category. There were 4,955 CI and 4,620 ICSI retrievals. The smallest groups were time category 7 and 0 for CI and ICSI respectively. The results showed that the mean fertilization rate per egg retrieved for CI ranged from 54.1 to 64.9% with a significant difference between time category 0 and 5 (p < 0.001) and category 1 and 5 (p < 0.0.001). Mean fertilization rate for ICSI per egg retrieved ranged from 52.8 to 67.3% with no significant difference between time categories compared to category 5. Blastocyst utilization rate for CI and ICSI were not significantly different for all time categories. In the CI and ICSI groups there were 6,540 and 6,178 total fresh and frozen transfers. The miscarriage and clinical pregnancy rate in CI and ICSI were not significantly different across time categories. The overall mean live birth rate for CI was 32.4% (range: 23.1 to 35.5%). Live-birth rates differed significantly (p = 0.04) in CI with time categories 0 and 7 the lowest. In the ICSI group, the overall mean live birth rate was 30.8% (range: 29.1 to 35.7%),with no significant differences between time categories. Limitations, reasons for caution As this is a retrospective study, the influence of uncontrolled variables cannot be excluded. The group spread was uneven with the early and late time categories having the lowest number of representative retrievals and this could have affected the results obtained. Wider implications of the findings: Our results indicate that both CI and ICSI are optimal when performed between 1.5–6.5 hours after oocyte retrieval. Further prospective studies on reproductive outcomes related to time of insemination are warranted. This data indicates a minimal detrimental effect when it is untenable to follow strict insemination time intervals. Trial registration number 2015P000122


PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0206067 ◽  
Author(s):  
Mathilde Bourdon ◽  
Pietro Santulli ◽  
Chloé Maignien ◽  
Khaled Pocate-Cheriet ◽  
Asim Alwohaibi ◽  
...  

2021 ◽  
Author(s):  
Giovanni Coticchio ◽  
Kenji Ezoe ◽  
Cristina Lagalla ◽  
Kiyoe Shimazaki ◽  
Kazuki Ohata ◽  
...  

Abstract STUDY QUESTION Do perturbations of embryo morphogenesis at compaction affect blastocyst development and clinical outcomes in assisted reproduction cycles? SUMMARY ANSWER Cell exclusion and extrusion, i.e. cell disposal occurring respectively before or during morula compaction, affect blastocyst yield and quality, as well as rates of pregnancy and live birth. WHAT IS KNOWN ALREADY Despite its pivotal role in morphogenesis for blastocyst organisation and cell fate determination, compaction at the morula stage has received little attention in clinical embryology. Time lapse technology (TLT) allows detailed morphokinetic analysis of this developmental stage. However, even in the vast majority of previous TLT studies, compaction was investigated without a specific focus. Recently, we reported that compaction may be affected by two clearly-distinct patterns of cell disposal, exclusion and extrusion, occurring prior to and during compaction, respectively. However, the crucial question of the specific relevance of partial compaction for embryo development and competence in ART has remained unanswered until now. STUDY DESIGN, SIZE, DURATION This study involved the assessment of laboratory and clinical outcomes of 2,059 morula stage embryos associated with 1,117 ICSI patients, who were treated with minimal stimulation and single vitrified-warmed blastocyst transfer (SVBT) from April 2017 to March 2018. Patterns of morula compaction were assessed and analyzed in relation to embryonic and clinical outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS Following ICSI, time-lapse videos were analysed to annotate morphokinetic parameters relevant to both pre- and post-compaction stages. According to their morphokinetic history, morulae were classified as: (I) fully compacted morulae (FCM); (II) partially compacted morulae (PCM), showing cells (a) excluded from the compaction process from the outset (Exc-PCM), (b) extruded from an already compacted morula (Ext-PCM), or (c) showing non-compacted cells arisen from both patterns (Exc/Ext-PCM). The number of excluded/extruded cells was also annotated. Possible correlations of compaction patterns with 13 morphokinetic parameters, abnormal cleavage, blastocyst yield and morphological grade, clinical and ongoing pregnancy rates, and live birth rate were evaluated. Other factors, such as patient and cycle characteristics, possibly associated with compaction patterns and their outcomes, were investigated. MAIN RESULTS AND THE ROLE OF CHANCE Full compaction was observed in 39.0% of all embryos. However, partially compacted morulae (PCM) showing excluded (Exc-PCM), extruded (Ext-PCM) cells, or indeed both phenotypes (Exc/Ext-PCM) were frequently detected (24.8%, 16.6%, and 19.6%, respectively) and collectively (61%) exceeded fully compacted morulae. Blastomere exclusion or extrusion affected one or several cells, in different proportions. In comparison to FCM, the developmental pace of the three PCM groups, observed at 13 developmental stages starting from pronuclear fading, was progressively slower (P < 0.0001). Developmental delay at post-compaction stages was more pronounced in the group showing both patterns of partial compaction. Blastomere exclusion and/or extrusion had a large negative impact on blastocyst development. In particular, rates of blastocyst formation and cryopreservation were very low in the Ext-PCM and Exc/Ext-PCM groups (P < 0.0001). Rates of blastocysts with ICM or TE of highest quality (Grade A) were severely affected in all PCM groups (P < 0.0001). In 1,083 SVBTs, blastocysts derived from all PCM groups produced much lower clinical pregnancy, ongoing pregnancy, and live birth rates (P < 0.0001). All three patterns of partial compaction emerged as factors independently associated with live birth rate, even after multivariate logistic regression analysis including maternal/paternal age, female BMI, and number of previous embryo transfers as possible confounding factors. LIMITATIONS, REASONS FOR CAUTION The retrospective design of the study represents a general limitation. WIDER IMPLICATIONS OF THE FINDINGS This large-scale study represents a further important demonstration of embryo plasticity and above all indicates new robust morphokinetic parameters for improved algorithms of embryo selection. STUDY FUNDING/COMPETING INTEREST(S) This study was exclusively supported by the participating institutions. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER NA.


2020 ◽  
Author(s):  
Shokichi Teramoto ◽  
Hisao Osada ◽  
Tsuyoshi Okubo ◽  
Tsuyoshi Ueno ◽  
Fumihito Aono ◽  
...  

Abstract Background: Diclofenac inhibits follicle rupture and its use in natural-cycle in vitro fertilization and embryo transfer (IVF-ET) has been reported to increase oocyte retrieval chances but has not been reported to improve the therapeutic outcome (live birth). The question is whether the therapeutic utility of diclofenac is demonstrable when administered to a subgroup of women with an imminent LH surge, a higher risk group for premature ovulation.Methods: Infertile women indicated for the natural-cycle IVF-ET between September 2014 and February 2015 (n=183) were recruited in a private infertility clinic and diclofenac use (50 mg suppositories, thrice every 8 h before oocyte retrieval) was offered when their serum LH level was ≥14.0 IU/L on an LH-triggering day (n=137). Of the 137 women, 108 electively used diclofenac and 29 did not. Oocytes were retrieved from both dominant and subordinate nondominant follicles and were fertilized. The resulting blastocysts were frozen, thawed, and transferred one by one in the following spontaneous ovulatory or hormone replacement cycles. Results: Cumulative live birth rate (after the single oocyte retrieval) was calculated from the dominant and nondominant follicles. The live birth rate from dominant follicles was higher in the diclofenac group (21/108, 19%) than in the no diclofenac group (1/29, 3%) (P < .05). Conversely, the live birth rate from nondominant follicles, which had no potential for ovulation, was not different between the diclofenac group (13/108, 12%) and the no diclofenac group (3/29, 10%). Conclusion: Diclofenac improved the live birth rate from dominant follicles when it was administered to women with an imminent LH surge. However, diclofenac did not affect the live birth rate from non-dominant follicles which were not at risk of follicle rupture.


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