P–781 Birthweight is not affected by freezing process. Results from a quasi-experimental study using the Oocyte Donation Model

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N Díaz ◽  
J Llácer ◽  
E Álvarez ◽  
E Serrano ◽  
J Ortiz ◽  
...  
Keyword(s):  
Sample Size ◽  
Embryo Transfer ◽  
Gestational Age ◽  
Endometrial Thickness ◽  
Large For Gestational Age ◽  
Freezing Process ◽  
Fresh Embryo Transfer ◽  
Term Birth ◽  
Quasi Experimental ◽  
Frozen Embryo Transfers

Abstract Study question Is the freezing process responsible to increase the birthweight or the incidence of Large for Gestational Age (LGA) in Frozen Embryo Transfers (FET)? Summary answer Neither the birthweight nor the LGA incidence were different in embryos that underwent the freezing-thawing process. What is known already Freezing-thawing constitutes one of the processes with a potential impact on the health of the newborn. Data coming from register-based studies and metaanalisis have found an increase in birthweight with a higher incidence of LGA in newborns coming from FET. This is a matter of concern since epigenetic alterations have been suggested to explain this finding casting doubts on future health during childhood and adulthood. Clarifying the safety of cryotechniques should be a priority taken into account that at present frozen embryo transfers outnumber fresh embryo transfers in IVF clinics. Study design, size, duration This retrospective cohort study evaluated 670 women oocyte recipients who underwent fresh (367 cycles) or frozen embryo transfer (303 cycles) at Instituto Bernabeu between July 2017 and March 2019. All recipients were prepared with substitutive cycle and received single blastocyst embryo transfers on day five. All of them at the same culture medium, resulting in a singleton live birth. Participants/materials, setting, methods 1637 patients were assessed for eligibility but 967 were excluded. The sample size has been calculated accepting an alpha risk of 5% and a beta risk of 20%. A sample size of 266 patients (133 per group) is required to detect a minimum mean difference of 275 grams with a standard deviation of 800 grams. Pearsońs Chi-square test (univariate) and binary logistic regression (multivariate for confounding factors) were used to analyze association between variables. Main results and the role of chance Maternal age (42.21 ± 4.45; 42.79 ± 3.83 p = 0.519), BMI (23.34 ± 3.69; 24.99 ± 15.52; p = 0.060), maternal parity (Nulliparous 81.5%; 85.5%; Multiparous 18.5%; 14.5% p = 0.177), gestational diabetes (4.9%; 4.3% p = 0.854), preeclampsia (2.7%; 5.6% p = 0.074), hypertensive disorders (3.3%; 2.3% p = 0.494), maternal smoking (10.8%; 13.0% p = 0.475), gestational age (38.96 ± 1.97; 38.77 ± 2.15; p = 0.207) and liveborn gender (Female 44.5%; 48.8%; Male 55.5%; 51.2%p=0.276) do not present statistically significant differences between fresh or frozen groups, respectively. However endometrial thickness was statistically signiticantly different in both groups (8.83mm ± 1.73 fresh; 8.57mm ± 1.59 frozen p = 0.035) The mean birthweight did not present statistically significant differences (3239.21 ± 550.43 fresh; 3224.56 ± 570.83 frozen p = 0.211). There were also no differences regarding macrosomy (7.1% fresh; 6.3% frozen p = 0.317), LGA (6.0% fresh; 6.7% frozen p = 0.866), pre-term birth (10.9% fresh; 9.0% frozen p = 0.988), very pre-term birth (0.8% fresh; 1.3% frozen p = 0.999), and extremely pre-term birth (0% fresh; 1.0% frozen p = 0.998). There were statistically significant differences regarding underweight (10.0% fresh; 7.0% frozen p = 0.020), but there were no differences in very low weight (0.6 fresh; 1.1% frozen p = 0.972) and SGA (1.9% fresh; 0.7% frozen p = 0.432). Limitations, reasons for caution Despite a quasi-experimental design, the synchronization in fresh embryo transfer drove to a longer preparation with a thicker endometrium. It’s not possible to rule-out the influence in the results of this parameter. Wider implications of the findings: As a hypothesis, the increase in birthweight and/or an abnormal placentation in FET could be explained by the endometrial preparation more than the freezing process. Studies must be planned in the future to explore the possibility of changes in the birthweight between embryos transferred in natural vs artificial endometrial preparations. Trial registration number Not applicable

The euploid blastocysts obtained after luteal phase stimulation show the same clinical, obstetric and perinatal outcomes as follicular phase stimulation-derived ones: a multicenter study

2020 ◽  
Vol 35 (11) ◽  
pp. 2598-2608
Author(s):  
Alberto Vaiarelli ◽  
Danilo Cimadomo ◽  
Erminia Alviggi ◽  
Anna Sansone ◽  
Elisabetta Trabucco ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Live Birth ◽  
Multicenter Study ◽  
Gestational Age ◽  
Ovarian Stimulation ◽  
Luteal Phase ◽  
Perinatal Outcomes ◽  
Follicular Phase ◽  
Blastocyst Transfer ◽  
Large For Gestational Age

Abstract STUDY QUESTION Are the reproductive outcomes (clinical, obstetric and perinatal) different between follicular phase stimulation (FPS)- and luteal phase stimulation (LPS)-derived euploid blastocysts? SUMMARY ANSWER No difference was observed between FPS- and LPS-derived euploid blastocysts after vitrified-warmed single embryo transfer (SET). WHAT IS KNOWN ALREADY Technical improvements in IVF allow the implementation non-conventional controlled ovarian stimulation (COS) protocols for oncologic and poor prognosis patients. One of these protocols begins LPS 5 days after FPS is ended (DuoStim). Although, several studies have reported similar embryological outcomes (e.g. fertilization, blastulation, euploidy) between FPS- and LPS-derived cohort of oocytes, information on the reproductive (clinical, obstetric and perinatal) outcomes of LPS-derived blastocysts is limited to small and retrospective studies. STUDY DESIGN, SIZE, DURATION Multicenter study conducted between October 2015 and March 2019 including all vitrified-warmed euploid single blastocyst transfers after DuoStim. Only first transfers of good quality blastocysts (≥BB according to Gardner and Schoolcraft’s classification) were included. If euploid blastocysts obtained after both FPS and LPS were available the embryo to transfer was chosen blindly. The primary outcome was the live birth rate (LBR) per vitrified-warmed single euploid blastocyst transfer in the two groups. To achieve 80% power (α = 0.05) to rule-out a 15% difference in the LBR, a total of 366 first transfers were required. Every other clinical, as well as obstetric and perinatal outcomes, were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS Throughout the study period, 827 patients concluded a DuoStim cycle and among them, 339 did not identify any transferable blastocyst, 145 had an euploid blastocyst after FPS, 186 after LPS and 157 after both FPS and LPS. Fifty transfers of poor quality euploid blastocysts were excluded and 49 patients did not undergo an embryo transfer during the study period. Thus, 389 patients had a vitrified-warmed SET of a good quality euploid blastocyst (182 after FPS and 207 after LPS). For 126 cases (32%) where both FPS- and LPS-derived good quality blastocysts were available, the embryo transferred was chosen blindly with a ‘True Random Number Generator’ function where ‘0’ stood for FPS-derived euploid blastocysts and ‘1’ for LPS-derived ones (n = 70 and 56, respectively) on the website random.org. All embryos were obtained with the same ovarian stimulation protocol in FPS and LPS (GnRH antagonist protocol with fixed dose of rec-FSH plus rec-LH and GnRH-agonist trigger), culture conditions (continuous culture in a humidified atmosphere with 37°C, 6% CO2 and 5% O2) and laboratory protocols (ICSI, trophectoderm biopsy in Day 5–7 without assisted hatching in Day 3, vitrification and comprehensive chromosome testing). The women whose embryos were included had similar age (FPS: 38.5 ± 3.1 and LPS: 38.5 ± 3.2 years), prevalence of male factor, antral follicle count, basal hormonal characteristics, main cause of infertility and previous reproductive history (i.e. previous live births, miscarriages and implantation failures) whether the embryo came from FPS or LPS. All transfers were conducted after warming in an artificial cycle. The blastocysts transferred after FPS and LPS were similar in terms of day of full-development and morphological quality. MAIN RESULTS AND THE ROLE OF CHANCE The positive pregnancy test rates for FPS- and LPS-derived euploid blastocysts were 57% and 62%, biochemical pregnancy loss rates were 10% and 8%, miscarriage rates were 15% and 14% and LBRs were 44% (n = 80/182, 95% CI 37–51%) and 49% (n = 102/207, 95% CI 42–56%; P = 0.3), respectively. The overall odds ratio for live birth (LPS vs FPS (reference)) adjusted for day of blastocyst development and quality, was 1.3, 95% CI 0.8–2.0, P = 0.2. Among patients with euploid blastocysts obtained following both FPS and LPS, the LBRs were also similar (53% (n = 37/70, 95% CI 41–65%) and 48% (n = 27/56, 95% CI 35–62%) respectively; P = 0.7). Gestational issues were experienced by 7.5% of pregnant women after FPS- and 10% of women following LPS-derived euploid single blastocyst transfer. Perinatal issues were reported in 5% and 0% of the FPS- and LPS-derived newborns, respectively. The gestational weeks and birthweight were similar in the two groups. A 5% pre-term delivery rate was reported in both groups. A low birthweight was registered in 2.5% and 5% of the newborns, while 4% and 7% showed high birthweight, in FPS- and LPS-derived euploid blastocyst, respectively. Encompassing the 81 FPS-derived newborns, a total of 9% were small and 11% large for gestational age. Among the 102 LPS-derived newborns, 8% were small and 6% large for gestational age. No significant difference was reported for all these comparisons. LIMITATIONS, REASONS FOR CAUTION The LPS-derived blastocysts were all obtained after FPS in a DuoStim protocol. Therefore, studies are required with LPS-only, late-FPS and random start approaches. The study is powered to assess differences in the LBR per embryo transfer, therefore obstetric and perinatal outcomes should be considered observational. Although prospective, the study was not registered. WIDER IMPLICATIONS OF THE FINDINGS This study represents a further backing of the safety of non-conventional COS protocols. Therefore, LPS after FPS (DuoStim protocol) is confirmed a feasible and efficient approach also from clinical, obstetric and perinatal perspectives, targeted at patients who need to reach the transfer of an euploid blastocyst in the shortest timeframe possible due to reasons such as cancer, advanced maternal age and/or reduced ovarian reserve and poor ovarian response. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER N/A.

Effects of maternal exposure to acute stress on birth outcomes: a quasi-experiment study

2021 ◽  
pp. 1-12
Author(s):  
Asma Ahmed ◽  
Suzanne King ◽  
Guillaume Elgbeili ◽  
David P. Laplante ◽  
Seungmi Yang
Keyword(s):  
Birth Outcomes ◽  
Gestational Age ◽  
Acute Stress ◽  
Maternal Stress ◽  
Population Based ◽  
Substantial Effect ◽  
Maternal Exposure ◽  
Large For Gestational Age ◽  
Ice Storm ◽  
Quasi Experimental

Abstract Numerous studies have shown associations between maternal stress and poor birth outcomes, but evidence is unclear for causal inference. Natural disasters provide an opportunity to study effects of quasi-randomized hardship with an accurate measure of onset and duration. In a population-based quasi-experimental study, we examined the effect of maternal exposure to the January 1998 Québec ice storm on birth outcomes by comparing pregnant mothers who lived in an area hard hit by the ice storm with those in two unaffected regions. In a total of 147,349 singleton births between 1995 and 2001, we used a difference-in-differences method to estimate the effects of the ice storm on gestational age at delivery (GA), preterm birth (PTB), weight-for-gestational-age z-scores (BWZ), large for gestational age (LGA), and small for gestational age (SGA). After adjusting for maternal and sociodemographic characteristics, there were no differences between the exposed and the unexposed mothers for birth outcomes. The estimated differences (exposed vs. unexposed) were 0.01 SDs (95% CI: −0.02, 0.05) for BWZ; 0.10% point (95% CI: −0.95%, 1.16%) for SGA; 0.25% point (95% CI: −0.78%, 1.28%) for LGA; −0.01 week (95% CI: −0.07, 0.05) for GA; and 0.16% point (95% CI: −0.66%, 0.97%) for PTB. Neither trimester-specific nor dose–response associations were observed. Overall, exposure to the 1998 Québec ice storm as a proxy for acute maternal stress in pregnancy was not associated with poor birth outcomes. Our results suggest that acute maternal hardship may not have a substantial effect on adverse birth outcomes.

Effect of endometrial thickness on birthweight in frozen embryo transfer cycles: an analysis including 6181 singleton newborns

2019 ◽  
Vol 34 (9) ◽  
pp. 1707-1715 ◽  
Author(s):  
Jie Zhang ◽  
Hongfang Liu ◽  
Xiaoyan Mao ◽  
Qiuju Chen ◽  
JiQiang Si ◽  
...  
Keyword(s):  
Linear Regression ◽  
Embryo Transfer ◽  
Gestational Age ◽  
Endometrial Thickness ◽  
Linear Regression Analysis ◽  
Tertiary Care ◽  
Frozen Embryo Transfer ◽  
Z Scores ◽  
The Impact ◽  
The Relationship

Abstract STUDY QUESTION Does endometrial thickness (EMT) have an impact on singleton birthweight in frozen embryo transfer (FET) cycles? SUMMARY ANSWER An EMT <8 mm was associated with a lower mean birthweight and gestational age- and gender-adjusted birthweight (Z-scores) of singletons resulting from FET. WHAT IS KNOWN ALREADY Previous studies have examined the impact of EMT on IVF success rates. Little is known, however, regarding the relationship between EMT and neonatal birthweight. STUDY DESIGN, SIZE, DURATION This retrospective study involved singleton live births born to women undergoing frozen-thawed Day 3 embryo transfer during the period from January 2010 to December 2017 at a tertiary care centre. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 6181 women who fulfilled the inclusion criteria were included and were grouped into five groups depending on the EMT: <8 mm, 8–9.9 mm, 10–11.9 mm, 12–13.9 mm and ≥14 mm. EMT between 10 and 11.9 mm was taken as a reference group. Singleton birthweight was the primary outcome measure. A multivariable linear regression analysis was performed to detect a relationship between EMT and newborns' birthweight after controlling for a number of potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE A modest but significant decrease in birthweight was observed in the EMT <8 mm group as compared with groups with EMT ≥10 mm, with a mean difference of 89–108 g. Also, singletons from the EMT <8 mm group (0.24 ± 1.04) had a significantly lower birthweight Z-scores than those from the EMT 10–11.9 mm (0.41 ± 1.02; P = 0.032) or EMT 12–13.9 mm (0.46 ± 1.07; P = 0.004) groups. Further, multiple linear regression analyses indicated that parental BMIs, gestational age, newborn gender, pregnancy complications and EMT <8 mm were all independent predictors of neonatal birthweight. LIMITATIONS, REASONS FOR CAUTION The present study was limited by its retrospective design. Future prospective studies are required to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS Our findings provided new insight into the relationship between EMT and neonatal outcomes by showing that a thin endometrium is associated with a decrease in singleton birthweight. STUDY FUNDING/COMPETING INTEREST(S) National Key Research and Development Program of China (2018YFC1003000); the National Natural Science Foundation of China (81771533, 81571397, 31770989, 81671520); the China Postdoctoral Science Foundation (2018M630456). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER Not applicable.

P–325 The impact of letrozole on endometrial thickness in IVF cycles

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J Ruiter-Ligeti ◽  
S Arab ◽  
W Buckett
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Fertility Preservation ◽  
Embryo Transfer ◽  
Endometrial Thickness ◽  
Oocyte Retrieval ◽  
Estradiol Level ◽  
Poor Responders ◽  
Fresh Embryo Transfer ◽  
The Impact

Abstract Study question Does daily administration of letrozole during IVF stimulation affect endometrial thickness ? Summary answer Patients treated with letrozole during fresh IVF cycles had a thinner endometrium on the day of trigger compared to patients who did not receive letrozole. What is known already Letrozole supplementation is commonly used during fertility preservation for breast cancer patients to reduce peak estrogen levels with no adverse effects on embryo outcomes. Studies in poor responders have found that letrozole use resulted in a shorter duration of stimulation and a lower total dose of gonadotropin, with no detrimental effect on IVF outcomes. In normal responders, studies have shown an increase in blastocysts obtained, but have not yet shown an increase in clinical pregnancy rates. There is concern that when a fresh embryo transfer is planned letrozole use may negatively affect endometrial thickness and subsequently diminish pregnancy rates. Study design, size, duration In a retrospective cohort study between January 2009 and June 2019 at a single academic fertility center, we compared the endometrial thickness in 97 cancer patients who underwent IVF-fertility preservation with daily letrozole use to 158 cancer patients who underwent IVF-fertility preservation without letrozole. Participants/materials, setting, methods All women diagnosed with cancer were referred for fertility preservation prior to gonadotoxic treatment exposure and were less than 40 years old at the time of oocyte retrieval. All patients who received letrozole started on day one of stimulation and continued until the day of oocyte retrieval. The primary outcome was endometrial thickness on the day of trigger. The secondary outcomes were number of oocytes retrieved, number of MII retrieved, and maximal estradiol level. Main results and the role of chance During the study period, 336 cancer patients underwent fertility preservation. Eighty-one patients were excluded; 50 because they had an intrauterine device or were on long term oral contraceptives and 31 because endometrial thickness was not documented. Of the remaining 255 patients, 86 had breast cancer, 95 had a hematological cancer and 74 had various other cancers. Ninety-seven cancer patients treated with letrozole were compared to 158 cancer patients who did not receive letrozole. Patients who received letrozole were significantly older (34 vs 28yrs, P &lt; 0.0001). There were no significant differences in baseline characteristics such as BMI, AFC nor in the total duration for stimulation. Endometrial thickness on the day of trigger was significantly less in letrozole treated patients (8 vs 9mm, P &lt; 0.003). There were no significant differences in total number of oocytes retrieved (12.5 vs 11, P = 0.126) nor in the number of mature oocytes (8 vs 8, P = 0.312). Patients in the letrozole group received a higher total gonadotropin dose (2680IU vs 1980IU, P = 0.016). The maximum estradiol level was significantly lower in patients treated with letrozole (1068 vs 3838ml/dl, P = &lt;0.0001). A regression analysis showed that using letrozole during stimulation decreased the endometrial thickness by 0.81mm (CI –1.37 to –0.253, P = 0.005). Limitations, reasons for caution The retrospective nature of this study could have introduced selection and misinformation bias. We report on cancer patients where all oocytes or embryos were vitrified. Without fresh embryo transfer data, it is unclear if a thinner endometrium due to letrozole will effect the implantation or pregnancy rate. Wider implications of the findings: As the use of letrozole expands beyond cancer patients and poor responders, it is important to understand the impact on the endometrium. This study shows that letrozole reduces endometrial thickness. However, the effect on endometrial function remains unknown. Further study is needed before letrozole can be used with fresh transfers. Trial registration number 2020–6370

Risk of small for gestational age is reduced after frozen compared with fresh embryo transfer in endometriosis

2020 ◽  
Author(s):  
Mathilde Bourdon ◽  
Pietro Santulli ◽  
Lauren Sebbag ◽  
Chloé Maignien ◽  
Francois Goffinet ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Fresh Embryo Transfer

P–765 Embryo donation pregnancies are at high risk even in young recipients

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Peigné ◽  
J D Mouzon ◽  
A Kiehl ◽  
A Fraissinet ◽  
V Maget ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Gestational Age ◽  
Large For Gestational Age ◽  
Embryo Cryopreservation ◽  
Control Group ◽  
Delivery Mode ◽  
Embryo Donation ◽  
And Control ◽  
Frozen Thawed Embryo Transfer ◽  
Thawed Embryo Transfer

Abstract Study question Are pregnancies after embryo donation (ED) at higher risk of complications than those issued from autologous frozen-thawed embryo transfer (FET)? Summary answer Even in young women, the risk of pregnancy induced hypertension (PIH) is four time higher in pregnancies after ED versus controls. What is known already After oocyte donation, a higher risk of PIH is well described. It is more controversial after sperm donation. The risk origin remains uncertain, even though an immunological explanation seems most likely. In ED, the fetus being fully allogeneic to his parents may be less well-tolerated. Very few data are reported about pregnancies after ED. The same allogenic model exists in surrogacies, but pregnancy complications are not well described in the literature. Study design, size, duration This anonymous, multicenter, comparative observational retrospective cohort study included all singleton ED pregnancies diagnosed at 7–8 weeks, from January 2003 to December 2018, in six French ART centers. For each, two controls were matched among autologous FET pregnancies. 209 pregnancies were included: 73 ED and 136 controls. Multiple pregnancies were excluded because of their increased associated obstetrical risks. Participants/materials, setting, methods Controls were matched according to pregnancy date, parity and women’s age. The first two singleton pregnancies after each index case meeting the selection criteria were retained. Each center coordinator collected information on infertility, pregnancy pathologies, outcomes and newborns. Statistical methods included univariate and multivariate analyses. According to French practice, all women were under 44 y/o. The main outcome was the percentage of PIH for ED versus controls. Main results and the role of chance ED was indicated for genetic disease in 17 cases (23.3%), double total infertility in 28 cases (38.3%), and double partial/total infertility in 35 cases (47.9%). Groups were comparable in age (mean age: 34.5 ± 8.6 versus 34.5 ± 4.5; p = 0.68), BMI, except for parity (more nulliparity in ED group: 90.4% vs 79.4%; p = 0.04). Pregnancy outcomes were similar for ED and control groups, the percentages of deliveries being 80.8% and 83.8%, respectively (p = 0.58). PIH occurred significantly more frequently among ED than control pregnancies (24.6% versus 11.9%; P = 0.04), with the difference mainly observed for severe forms: preeclampsia and HELLP (17.5% vs 4.6%; p = 0.01). No eclampsia was reported. In contrast, isolated hypertension frequency was comparable (7.0% vs. 7.3%, p = 0.94). Regarding labor and delivery mode, in ED group C-section was more frequent (47.3% vs 29.2%; p = 0.03). In neonatal data, no difference was found between ED and control group for prematurity, weight and height at birth, Apgar score, Small for gestational age, Large for gestational age and sex ratio. Seven neonatal malformations were recorded in ED group and 3 in the control group (NS). Limitations, reasons for caution Retrospective study in a relatively long period when different endometrial preparation for frozen-thawed embryo transfer and embryo cryopreservation method were used. Relatively limited number of ED because of low practice in France. No analysis of embryo stage at transfer (cleaved embryo or blastocyst). Wider implications of the findings: The PIH risk must be acknowledged to inform couples and provide careful pregnancy monitoring. A special care for gestational carrier should also be done since the allogenic situation is the same than in ED recipients. Trial registration number Not applicable

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